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. 2009 Sep;135(9):1177-84.
doi: 10.1007/s00432-009-0558-8. Epub 2009 Feb 13.

Human cervical carcinoma xenograft models for studies of the physiological microenvironment of tumors

Christine Ellingsen  1 , Ingrid Natvig, Jon-Vidar Gaustad, Kristine Gulliksrud, Tormod A M Egeland, Einar K Rofstad
Affiliations

Human cervical carcinoma xenograft models for studies of the physiological microenvironment of tumors

Christine Ellingsen et al. J Cancer Res Clin Oncol. 2009 Sep.

Abstract

Objective: To establish and characterize experimental tumor models of advanced squamous cell carcinoma of the uterine cervix.

Methods: Permanent cell lines (CK-160 and TS-415) were established from pelvic lymph node metastases of two cervical carcinoma patients. Xenografted tumors were initiated by inoculating 5 x 10(5) cells into the gastrocnemius muscle of BALB/c nu/nu mice. The tumors were characterized with respect to histological appearance, fraction of necrotic tissue (NF), pimonidazole hypoxic fraction (HF(Pim)), interstitial fluid pressure (IFP), extracellular pH (pH(e)), metastatic propensity, and radiation sensitivity.

Results: The xenografted tumors reflected the donor patients' tumors in histological appearance, metastatic propensity, and radiation sensitivity and showed significant intertumor heterogeneity in growth rate, NF, HF(Pim), IFP, and pH(e).

Conclusions: CK-160 and TS-415 xenografts possess properties making them relevant models for studies of the physiological microenvironment of cervical carcinoma and its influence on metastatic dissemination and response to treatment.

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Figures

Fig. 1
Fig. 1
Volume doubling times of CK-160 and TS-415 tumors. Points represent individual tumors. Horizontal bars represent mean values
Fig. 2
Fig. 2
Immunohistochemical preparations of a CK-160 (a) and a TS-415 (b) tumor stained with anti-pimonidazole antibody to visualize regions with hypoxic tissue. Hypoxic regions appear dark brown
Fig. 3
Fig. 3
Fraction of hypoxic tissue (a) and fraction of necrotic tissue (b) in CK-160 and TS-415 tumors. Points represent individual tumors. Horizontal bars represent mean values
Fig. 4
Fig. 4
Interstitial fluid pressure (a) and extracellular pH (b) in CK-160 and TS-415 tumors. Points represent individual tumors. Horizontal bars represent mean values
Fig. 5
Fig. 5
Cell survival curves for CK-160 and TS-415 monolayer cultures irradiated under aerobic conditions in vitro (a) and CK-160 and TS-415 tumors irradiated under hypoxic conditions in vivo (b). Points and bars represent geometric mean ± standard error of five to eight cultures or tumors
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