Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivationviaarginine deiminase

Abstract

Material and methods Cell cultureRenal cell carcinoma cell lines (Caki-1, Caki-2, ACHN, SN12C, SN12PM6, RENCA) were purchased from Korean Cell

Arginine Deprivation as a Targeted Therapy for Cancer

“…Based on this study, clinical trials in mesothelioma have been initiated [Szlosarck, personal communication]. ADI-PEG20 is also active in certain renal cell cancer cell lines which do not express ASS [16]. Interestingly, some renal cell cancers also are negative for ASS by immunohistochemical staining despite high levels of these enzymes found in the kidney.…”

“…Thus, depletion of this amino acid by asparaginase therapy is generally well tolerated since normal human cells do not require asparagine. Thus, eliminating a certain Several laboratories have reported that certain tumor cell lines such as melanoma, hepatocellular carcinoma, renal cell carcinoma and some mesotheliomas do not express ASS, and hence become auxotrophic for arginine [9,11,[15][16][17][18]. Consequently, arginine degrading enzyme has been shown by several laboratories to have antitumor effect in these tumors [9,13,[19][20][21][22][23][24][25].…”

“…Furthermore, this enzyme is active in physiologic pH and has a high affinity for arginine. In fact, ADI has been reported to have antitumor activity both in vitro and in vivo in melanoma and hepatocellular carcinoma cell lines and in other cell lines [15][16][17][18][31][32][33][34]. However, one of the drawbacks of ADI is that it is not produced by humans and, consequently, it is highly antigenic.…”

Arginine enzymatic deprivation and diet restriction for cancer treatment

“…Citrulline can be recycled back to arginine in normal cells which express argininosuccinate synthetase (ASS), whereas ASS(-) tumor cells cannot. Loss of ASS expression has been most widely associated with melanoma and hepatocellular carcinoma, although it has now been identified in other tumor types including pancreatic cancer, leukemia, prostate cancer and renal cell carcinoma (Gong et al, 2000;Ensor et al, 2002;Yoon et al, 2007;Bowles et al, 2008;Kim et al, 2009).…”

“…Histological examination of the tumors revealed that tumor angiogenesis and vascular endothelial growth factor (VEGF) expression were significantly diminished by ADI administration (Yoon et al, 2007). Bowles et al (2008) evaluated the level of ASS expression in 47 human pancreatic adenocarcinoma specimens and 20 normal pancreas biopsies.…”