Immunoregulatory protein B7-H3 promotes growth and decreases sensitivity to therapy in metastatic melanoma cells

Pigment Cell & Melanoma Research
Karine Flem-KarlsenCaroline E Nunes-Xavier

Abstract

B7-H3 (CD276) belongs to the B7 family of immunoregulatory proteins and has been implicated in cancer progression and metastasis. In this study, we found that metastatic melanoma cells with knockdown expression of B7-H3 showed modest decrease in proliferation and glycolytic capacity and were more sensitive to dacarbazine (DTIC) chemotherapy and small-molecule inhibitors targeting MAP kinase (MAPK) and AKT/mTOR pathways: vemurafenib (PLX4032; BRAF inhibitor), binimetinib (MEK-162; MEK inhibitor), everolimus (RAD001; mTOR inhibitor), and triciribidine (API-2; AKT inhibitor). Similar effects were observed in melanoma cells in the presence of an inhibitory B7-H3 monoclonal antibody, while the opposite was seen in B7-H3-overexpressing cells. Further, combining B7-H3 inhibition with small-molecule inhibitors resulted in significantly increased antiproliferative effect in melanoma cells, as well as in BRAFV600E mutated cell lines derived from patient biopsies. Our findings indicate that targeting B7-H3 may be a novel alternative to improve current therapy of metastatic melanoma.

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Citations

Jun 22, 2019·Journal of Cellular Physiology·Xiangqi ZhouManbo Cai
Sep 27, 2019·Cancers·Malgorzata BobrowiczMagdalena Winiarska
Apr 11, 2019·Scientific Reports·Karine Flem-KarlsenCaroline E Nunes-Xavier
May 18, 2019·Current Medicinal Chemistry·Karine Flem-KarlsenCaroline E Nunes-Xavier
Jul 24, 2018·Frontiers in Oncology·Peixin DongHidemichi Watari
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Jul 14, 2020·Seminars in Cancer Biology·Ombretta MelaiuFederica Gemignani
Apr 3, 2021·Acta Neuropathologica Communications·Marina DigregorioBernard Rogister
May 25, 2021·Frontiers in Pharmacology·Jii Bum LeeHye Ryun Kim
Jul 3, 2021·International Journal of Molecular Sciences·Ying SunHao Hu
Aug 6, 2021·Frontiers in Immunology·Wu-Tong Zhou, Wei-Lin Jin
Aug 10, 2021·Frontiers in Oncology·Xi-Yang TangJin-Bo Zhao
Aug 30, 2021·The International Journal of Biochemistry & Cell Biology·Nourhan Abu-ShahbaOsama Azmy

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