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

  • Author(s): Kawaguchi, Kei
  • Han, Qinghong
  • Li, Shukuan
  • Tan, Yuying
  • Igarashi, Kentaro
  • Miyake, Kentaro
  • Kiyuna, Tasuku
  • Miyake, Masuyo
  • Chemielwski, Bartosz
  • Nelson, Scott D
  • Russell, Tara A
  • Dry, Sarah M
  • Li, Yunfeng
  • Singh, Arun S
  • Eckardt, Mark A
  • Unno, Michiaki
  • Eilber, Fritz C
  • Hoffman, Robert M
  • et al.
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.

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