Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells

Esha Madan^#^{1

2

3

4}, António M Palma^#^{5

6

7

8}, Vignesh Vudatha^#^{9

5

8}, Amit Kumar^#^{5

6

7}, Praveen Bhoopathi^#^{9

5}, Jochen Wilhelm^#^{10

11}, Tytus Bernas¹², Patrick C Martin¹³, Gaurav Bilolikar^{5

7}, Aenya Gogna¹⁴, Maria Leonor Peixoto^{8

15}, Isabelle Dreier¹¹, Thais Fenz Araujo¹⁶, Elena Garre¹⁶, Anna Gustafsson¹⁶, Kalpana Deepa Priya Dorayappan¹⁷, Narsimha Mamidi¹⁸, Zhaoyu Sun¹⁹, Michail Yekelchyk¹¹, Davide Accardi¹⁵, Amalie Lykke Olsen^{20

21}, Lin Lin^{20

21}, Asaf Ashkenazy Titelman^{22

23}, Michael Bianchi²⁴, Phil Jessmon²⁴, Elnaz Abbasi Farid^{25

26}, Anjan K Pradhan⁷, Lena Neufeld²⁷, Eilam Yeini²⁷, Santanu Maji^{6

7}, Christopher J Pelham²⁸, Hyobin Kim¹³, Daniel Oh¹³, Hans Olav Rolfsnes²⁹, Rita C Marques¹⁵, Amy Lu^{5

7}, Masaki Nagane³⁰, Sahil Chaudhary^{9

5}, Kartik Gupta^{9

5}, Keshav C Gogna^{9

5}, Ana Bigio¹⁵, Karthikeya Bhoopathi^{5

7}, Padmanabhan Mannangatti^{5

6

7}, K Gopinath Achary³¹, Javed Akhtar³¹, Sara Belião¹⁵, Swadesh Das^{5

6

7}, Isabel Correia³², Cláudia L da Silva⁸, Arsénio M Fialho⁸, Michael J Poellmann³³, Kaila Javius-Jones³³, Adam M Hawkridge^{5

34}, Sanya Pal³⁵, Kumari S Shree^{5

7}, Emad A Rakha^{36

37}, Sambhav Khurana^{5

7}, Gaoping Xiao³⁸, Dongyu Zhang^{9

5}, Arjun Rijal⁵, Charles Lyons⁵, Steven R Grossman³⁹, David P Turner^{9

5}, Raghavendra Pillappa⁴⁰, Karanvir Prakash⁴¹, Gaurav Gupta⁴², Gary L W G Robinson⁴³, Jennifer Koblinski^{5

44}, Hongjun Wang^{45

46}, Gita Singh⁴⁷, Sujay Singh⁴⁷, Sagar Rayamajhi⁴⁸, Manny D Bacolod⁴⁹, Hope Richards⁴⁴, Sadia Sayeed⁴⁴, Katherine P Klein⁵⁰, David Chelmow⁵⁰, Ronit Satchi-Fainaro^{27

51}, Karuppaiyah Selvendiran¹⁷, Denise Connolly^{52

53}, Frits Alan Thorsen²⁹, Rolf Bjerkvig^{29

54

55

56}, Kenneth P Nephew^{25

26}, Michael O Idowu^{44

57}, Mark P Kühnel^{58

59}, Christopher Moskaluk⁶⁰, Seungpyo Hong^{18

33

61}, William L Redmond¹⁹, Göran Landberg¹⁶, Antonio Lopez-Beltran^{15

62

63

64}, Andrew S Poklepovic^{5

65}, Arun Sanyal⁶⁶, Paul B Fisher^{5

6

7}, George M Church^{22

23}, Usha Menon⁶⁷, Ronny Drapkin⁶⁸, Andrew K Godwin^{48

69

70}, Yonglun Luo^{20

21}, Maximilian Ackermann^{71

72}, Alexandar Tzankov⁷³, Kirsten D Mertz⁷³, Danny Jonigk^{58

59}, Allan Tsung⁷⁴, David Sidransky^{75

76}, Jose Trevino^{9

5}, Arturo P Saavedra^{9

77}, Robert Winn^{9

5

78}, Kyoung Jae Won¹², Eduardo Moreno¹⁵, Rajan Gogna^{79

80

81

82}

Affiliations

¹ Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. esha.gogna@vcuhealth.org.
² Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA. esha.gogna@vcuhealth.org.
³ VCU Institute of Molecular Medicine, Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. esha.gogna@vcuhealth.org.
⁴ Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. esha.gogna@vcuhealth.org.
⁵ Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
⁶ VCU Institute of Molecular Medicine, Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
⁷ Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
⁸ Institute for Bioengineering and Biosciences (iBB), Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
⁹ Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
¹⁰ Institute for Lung Health (ILH), Universities Giessen & Marburg Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University Giessen, Giessen, Germany.
¹¹ Universities Giessen & Marburg Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.
¹² Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA.
¹³ Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁴ Collegiate School, Richmond, VA, USA.
¹⁵ Champalimaud Center for the Unknown, Lisbon, Portugal.
¹⁶ Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
¹⁷ Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹⁸ Wisconsin Center for NanoBioSystems, School of Pharmacy, University of Wisconsin, Madison, WI, USA.
¹⁹ Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
²⁰ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
²¹ Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
²² Department of Genetics, Harvard Medical School, Boston, MA, USA.
²³ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
²⁴ Empire Genomics Corp., Depew, NY, USA.
²⁵ Indiana University School of Medicine-Bloomington, Indiana University, Bloomington, IN, USA.
²⁶ Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA.
²⁷ Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
²⁸ Eurofins Panlabs, Inc., St. Charles, MO, USA.
²⁹ Molecular Imaging Center, Department of Biomedicine, University of Bergen, Bergen, Norway.
³⁰ Department of Biochemistry, School of Veterinary Medicine, Azabu University, Sagamihara, Japan.
³¹ IMGENEX India Pvt. Ltd., Bhubaneswar, India.
³² Centro de Química Estrutural, Institute of Molecular Sciences and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
³³ Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI, USA.
³⁴ Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA.
³⁵ Innomics Inc., Cambridge, MA, USA.
³⁶ Department of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, UK.
³⁷ Nottingham Breast Cancer Research Centre, School of Medicine, Academic Unit for Translational Medical Sciences, University of Nottingham, Nottingham, UK.
³⁸ Syd Labs, Inc., Hopkinton, MA, USA.
³⁹ Department of Internal Medicine, Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
⁴⁰ Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁴¹ Department of Orthopedic Surgery, Virginia Commonwealth University, Richmond, VA, USA.
⁴² VCU Division of Nephrology, Virginia Commonwealth University, VCU School of Medicine, Richmond, VA, USA.
⁴³ PhaseDesign Research, Framingham, MA, USA.
⁴⁴ Department of Pathology, Virginia Commonwealth University, Richmond, VA, USA.
⁴⁵ Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ, USA.
⁴⁶ Center for Healthcare Innovation, Stevens Institute of Technology, Hoboken, NJ, USA.
⁴⁷ Abeomics, Inc., San Diego, CA, USA.
⁴⁸ Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
⁴⁹ Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
⁵⁰ Department of Obstetrics and Gynecology, Virginia Commonwealth University, VCU School of Medicine, Richmond, VA, USA.
⁵¹ Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
⁵² Fox Chase Cancer Center Biosample Repository Facility, Philadelphia, PA, USA.
⁵³ Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁵⁴ NORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway.
⁵⁵ Department of Oncology, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.
⁵⁶ Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Key Laboratory of Brain Functional Remodeling, Shandong, China.
⁵⁷ Virginia Commonwealth University Health, Richmond, VA, USA.
⁵⁸ Institute of Pathology, RWTH Aachen University, Aachen, Germany.
⁵⁹ Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover Medical School, Hanover, Germany.
⁶⁰ Department of Pathology, University of Virginia, Charlottesville, VA, USA.
⁶¹ Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
⁶² Department of Morphological Sciences, Cordoba University Medical School, Cordoba, Spain.
⁶³ Departamento de Patología, Centro Clínico Champalimaud, Lisboa, Portugal.
⁶⁴ Department of Surgery, Cordoba University Medical School, Cordoba, Spain.
⁶⁵ Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
⁶⁶ Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
⁶⁷ MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.
⁶⁸ Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶⁹ Kansas Institute for Precision Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
⁷⁰ University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, USA.
⁷¹ Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
⁷² Institute of Pathology and Molecular Pathology, Helios University Clinic Wuppertal, University of Witten/Herdecke, Wuppertal, Germany.
⁷³ Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.
⁷⁴ Department of Surgery, Division of Surgical Oncology, University of Virginia, Charlottesville, VA, USA.
⁷⁵ Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
⁷⁶ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷⁷ Department of Dermatology, VCU School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
⁷⁸ Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, VCU School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
⁷⁹ Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. rajan.gogna@vcuhealth.org.
⁸⁰ Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA. rajan.gogna@vcuhealth.org.
⁸¹ VCU Institute of Molecular Medicine, Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. rajan.gogna@vcuhealth.org.
⁸² Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. rajan.gogna@vcuhealth.org.

^# Contributed equally.

PMID: 39653752
DOI: 10.1038/s41587-024-02453-3

Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells

Esha Madan et al. Nat Biotechnol. 2024.

. 2024 Dec 9.

doi: 10.1038/s41587-024-02453-3. Online ahead of print.

Authors

Affiliations

¹ Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. esha.gogna@vcuhealth.org.
² Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA. esha.gogna@vcuhealth.org.
³ VCU Institute of Molecular Medicine, Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. esha.gogna@vcuhealth.org.
⁴ Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. esha.gogna@vcuhealth.org.
⁵ Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
⁶ VCU Institute of Molecular Medicine, Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
⁷ Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
⁸ Institute for Bioengineering and Biosciences (iBB), Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
⁹ Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
¹⁰ Institute for Lung Health (ILH), Universities Giessen & Marburg Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University Giessen, Giessen, Germany.
¹¹ Universities Giessen & Marburg Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.
¹² Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA.
¹³ Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁴ Collegiate School, Richmond, VA, USA.
¹⁵ Champalimaud Center for the Unknown, Lisbon, Portugal.
¹⁶ Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
¹⁷ Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹⁸ Wisconsin Center for NanoBioSystems, School of Pharmacy, University of Wisconsin, Madison, WI, USA.
¹⁹ Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
²⁰ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
²¹ Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
²² Department of Genetics, Harvard Medical School, Boston, MA, USA.
²³ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
²⁴ Empire Genomics Corp., Depew, NY, USA.
²⁵ Indiana University School of Medicine-Bloomington, Indiana University, Bloomington, IN, USA.
²⁶ Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA.
²⁷ Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
²⁸ Eurofins Panlabs, Inc., St. Charles, MO, USA.
²⁹ Molecular Imaging Center, Department of Biomedicine, University of Bergen, Bergen, Norway.
³⁰ Department of Biochemistry, School of Veterinary Medicine, Azabu University, Sagamihara, Japan.
³¹ IMGENEX India Pvt. Ltd., Bhubaneswar, India.
³² Centro de Química Estrutural, Institute of Molecular Sciences and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
³³ Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI, USA.
³⁴ Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA.
³⁵ Innomics Inc., Cambridge, MA, USA.
³⁶ Department of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, UK.
³⁷ Nottingham Breast Cancer Research Centre, School of Medicine, Academic Unit for Translational Medical Sciences, University of Nottingham, Nottingham, UK.
³⁸ Syd Labs, Inc., Hopkinton, MA, USA.
³⁹ Department of Internal Medicine, Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
⁴⁰ Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁴¹ Department of Orthopedic Surgery, Virginia Commonwealth University, Richmond, VA, USA.
⁴² VCU Division of Nephrology, Virginia Commonwealth University, VCU School of Medicine, Richmond, VA, USA.
⁴³ PhaseDesign Research, Framingham, MA, USA.
⁴⁴ Department of Pathology, Virginia Commonwealth University, Richmond, VA, USA.
⁴⁵ Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ, USA.
⁴⁶ Center for Healthcare Innovation, Stevens Institute of Technology, Hoboken, NJ, USA.
⁴⁷ Abeomics, Inc., San Diego, CA, USA.
⁴⁸ Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
⁴⁹ Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
⁵⁰ Department of Obstetrics and Gynecology, Virginia Commonwealth University, VCU School of Medicine, Richmond, VA, USA.
⁵¹ Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
⁵² Fox Chase Cancer Center Biosample Repository Facility, Philadelphia, PA, USA.
⁵³ Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁵⁴ NORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway.
⁵⁵ Department of Oncology, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.
⁵⁶ Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Key Laboratory of Brain Functional Remodeling, Shandong, China.
⁵⁷ Virginia Commonwealth University Health, Richmond, VA, USA.
⁵⁸ Institute of Pathology, RWTH Aachen University, Aachen, Germany.
⁵⁹ Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover Medical School, Hanover, Germany.
⁶⁰ Department of Pathology, University of Virginia, Charlottesville, VA, USA.
⁶¹ Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
⁶² Department of Morphological Sciences, Cordoba University Medical School, Cordoba, Spain.
⁶³ Departamento de Patología, Centro Clínico Champalimaud, Lisboa, Portugal.
⁶⁴ Department of Surgery, Cordoba University Medical School, Cordoba, Spain.
⁶⁵ Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
⁶⁶ Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
⁶⁷ MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.
⁶⁸ Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶⁹ Kansas Institute for Precision Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
⁷⁰ University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, USA.
⁷¹ Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
⁷² Institute of Pathology and Molecular Pathology, Helios University Clinic Wuppertal, University of Witten/Herdecke, Wuppertal, Germany.
⁷³ Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.
⁷⁴ Department of Surgery, Division of Surgical Oncology, University of Virginia, Charlottesville, VA, USA.
⁷⁵ Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
⁷⁶ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷⁷ Department of Dermatology, VCU School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
⁷⁸ Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, VCU School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
⁷⁹ Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. rajan.gogna@vcuhealth.org.
⁸⁰ Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA. rajan.gogna@vcuhealth.org.
⁸¹ VCU Institute of Molecular Medicine, Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. rajan.gogna@vcuhealth.org.
⁸² Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. rajan.gogna@vcuhealth.org.

^# Contributed equally.

PMID: 39653752
DOI: 10.1038/s41587-024-02453-3

Abstract

Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonstrate that the expression of Flower Lose and reduced microenvironment fitness is not a pre-existing condition but, rather, a cancer-induced phenomenon. Cancer cells actively reduce TME fitness by the exosome-mediated release of a cancer-specific long non-coding RNA, Tu-Stroma, which controls the splicing of the Flower gene in the TME cells and expression of Flower Lose isoform, which leads to reduced fitness status. This mechanism controls cancer growth, metastasis and host survival in ovarian cancer. Targeting Flower protein with humanized monoclonal antibody (mAb) in mice significantly reduces cancer growth and metastasis and improves survival. Pre-treatment with Flower mAb protects intraperitoneal organs from developing lesions despite the presence of aggressive tumor cells.

PubMed Disclaimer

Conflict of interest statement

Competing interests: All authors declare no competing interests.

References

1. Merino, M. M. et al. Elimination of unfit cells maintains tissue health and prolongs lifespan. Cell 160, 461–476 (2015). - PubMed - PMC - DOI
1. Merino, M. M., Rhiner, C., Portela, M. & Moreno, E. ‘Fitness fingerprints’ mediate physiological culling of unwanted neurons in Drosophila. Curr. Biol. 23, 1300–1309 (2013). - PubMed - DOI
1. Rhiner, C. et al. Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev. Cell 18, 985–998 (2010). - PubMed - DOI
1. Madan, E. et al. Flower isoforms promote competitive growth in cancer. Nature 572, 260–264 (2019). - PubMed - DOI
1. Yekelchyk, M. et al. Flower lose, a cell fitness marker, predicts COVID-19 prognosis. EMBO Mol. Med. 13, e13714 (2021). - PubMed - PMC - DOI

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells

Affiliations

Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Miscellaneous