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. 2018 Jan 17;9(13):11119-11125.
doi: 10.18632/oncotarget.24264. eCollection 2018 Feb 16.

Intra-tumor L-methionine level highly correlates with tumor size in both pancreatic cancer and melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse models

Kei Kawaguchi  1   2   3 , Qinghong Han  1 , Shukuan Li  1 , Yuying Tan  1 , Kentaro Igarashi  1   2 , Kentaro Miyake  1   2 , Tasuku Kiyuna  1   2 , Masuyo Miyake  1   2 , Bartosz Chemielwski  4 , Scott D Nelson  5 , Tara A Russell  6 , Sarah M Dry  5 , Yunfeng Li  5 , Arun S Singh  4 , Mark A Eckardt  7 , Michiaki Unno  3 , Fritz C Eilber  6 , Robert M Hoffman  1   2
Affiliations

Intra-tumor L-methionine level highly correlates with tumor size in both pancreatic cancer and melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse models

Kei Kawaguchi et al. Oncotarget. .

Abstract

An excessive requirement for methionine (MET) for growth, termed MET dependence, appears to be a general metabolic defect in cancer. We have previously shown that cancer-cell growth can be selectively arrested by MET restriction such as with recombinant methioninase (rMETase). In the present study, we utilized patient-derived orthotopic xenograft (PDOX) nude mouse models with pancreatic cancer or melanoma to determine the relationship between intra-tumor MET level and tumor size. After the tumors grew to 100 mm3, the PDOX nude mice were divided into two groups: untreated control and treated with rMETase (100 units, i.p., 14 consecutive days). On day 14 from initiation of treatment, intra-tumor MET levels were measured and found to highly correlate with tumor volume, both in the pancreatic cancer PDOX (p<0.0001, R2=0.89016) and melanoma PDOX (p<0.0001, R2=0.88114). Tumors with low concentration of MET were smaller. The present results demonstrates that patient tumors are highly dependent on MET for growth and that rMETase effectively lowers tumor MET.

Keywords: melanoma; methionine dependence; pancreatic cancer; recombinant methionine (rMETase); tumor methionine.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Correlation between tumor volume and intra-tumor MET level in the pancreatic cancer PDOX
Blue box: untreated controls; Red box: treated with rMETase. Please see the Materials and Methods for details.
Figure 2
Figure 2. Correlation between tumor volume and intra-tumor MET level in the melanoma PDOX
Blue box: untreated controls; Red box: treated with rMETase. Please see the Materials and Methods for details.
See this image and copyright information in PMC

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