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, Qinghong Han, Shukuan Li, Yuying Tan, Kentaro Igarashi, Kentaro Miyake, Tasuku Kiyuna, Masuyo Miyake, Bartosz Chemielwski, Scott D. Nelson, Tara A. Russell, Sarah M. Dry, Yunfeng Li, Arun S. Singh, Mark A. Eckardt, Michiaki Unno, Fritz C. Eilber, Robert M. Hoffman

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16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)11119-11125
Number of pages7
JournalOncotarget
Volume9
Issue number13
DOIs
Publication statusPublished - 2018

Keywords

  • Melanoma
  • Methionine dependence
  • Pancreatic cancer
  • Recombinant methionine (rMETase)
  • Tumor methionine

ASJC Scopus subject areas

  • Oncology

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    Kawaguchi, K., Han, Q., Li, S., Tan, Y., Igarashi, K., Miyake, K., Kiyuna, T., Miyake, M., Chemielwski, B., Nelson, S. D., Russell, T. A., Dry, S. M., Li, Y., Singh, A. S., Eckardt, M. A., Unno, M., Eilber, F. C., & Hoffman, R. M. (2018). Intra-tumor L-methionine level highly correlates with tumor size in both pancreatic cancer and melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse models. Oncotarget, 9(13), 11119-11125. https://doi.org/10.18632/oncotarget.24264