Stromal CD38 regulates outgrowth of primary melanoma and generation of spontaneous metastasis

Oncotarget
Bar Ben BaruchReuven Stein

Abstract

The outgrowth of primary melanoma, the deadliest skin cancer, and generation of metastasis is supported by the tumor microenvironment (TME) which includes non-cancerous cells. Since the TME plays an important role in melanoma pathogenesis, its targeting is a promising therapeutic approach. Thus, it is important to identify proteins in the melanoma TME that may serve as therapeutic targets. Here we show that the nicotinamide adenine dinucleotide glycohydrolase CD38 is a suitable target for this purpose. Loss of CD38 in the TME as well as inhibition of its enzymatic activity restrained outgrowth of primary melanoma generated by two transplantable models of melanoma, B16F10 and Ret-mCherry-sorted (RMS) melanoma cells. Pathological analysis indicated that loss of CD38 increased cell death and reduced the amount of cancer-associated fibroblasts (CAFs) and blood vessels. Importantly, in addition to inhibiting outgrowth of primary melanoma tumors, loss of CD38 also inhibited spontaneous occurrence of RMS pulmonary and brain metastasis. The underlying mechanism may involve, at least in the brain, inhibition of metastasis expansion, since loss of CD38 inhibited the outgrowth of B16F10 and RMS brain tumors that were generated by direct i...Continue Reading

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Citations

Jul 3, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Bar Ben BaruchReuven Stein
Nov 17, 2020·International Journal of Cancer. Journal International Du Cancer·Sarah DellacMarcelo Ehrlich
Feb 26, 2021·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Hajime KurodaAtsuko Masunaga
Mar 18, 2021·Journal of Oncology·Sanyog DwivediLuis F Montaño

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