Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MCAM/MUC18 expression correlates with tumor thickness and metastatic potential of human melanoma cells in nude mice. Moreover, ectopic expression of MUC18 in primary cutaneous melanoma cells leads to increased tumor growth and metastasis in vivo. Here we tested the effect of a fully human anti-MUC18 antibody, ABX-MA1, on angiogenesis, tumor growth, and metastasis. ABX-MA1 had no effect on melanoma cell proliferation rate in vitro. However, when cells of the metastatic melanoma lines A375SM and WM2664 (which express high levels of MUC18) were injected s.c. into nude mice and treated with ABX-MA1 (100 micro g, weekly, i.p. for 5 weeks), tumor growth was significantly inhibited compared with control IgG-treated mice. ABX-MA1 treatment also suppressed experimental lung metastasis of these melanoma cells. ABX-MA1 disrupted spheroid formation by melanoma cells expressing MUC18 (homotypic interaction) and the ability of these cells to attach to human vascular endothelial cells [HUVECs (MUC18 positive)] in vitro. ABX-MA1 treatment of melanoma cells in vitro significantly inhibited the promoter and collagenase activity of matrix metalloproteinase 2, resulting in decreased invasion through Matrigel-coated filters. Decreased expression of matrix metalloproteinase 2 was also observed in the implanted tumors in vivo. Moreover, because HUVECs also express MUC18, ABX-MA1 directly disrupted the tube-like formation by HUVECs in an in vitro vessel formation assay. Collectively, these results point to usefulness of ABX-MA1 as a modality to treat melanoma either alone or in combination with conventional chemotherapy or other antitumor agents.
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PMID:Fully human antibodies to MCAM/MUC18 inhibit tumor growth and metastasis of human melanoma. 1220 68

Metastatic melanoma is associated with high rate of patients' mortality and represents a great challenge for cancer therapies because of its notorious resistance to chemotherapeutic drugs. Considerable efforts have been made over the last 2 decades in pursuit of new treatment modalities and identification of molecular events associated with melanoma progression and development of metastases. The acquisition of the metastatic phenotype is associated with overexpression of the adhesion molecule MCAM/MUC18 and the angiogenic factor IL-8. In this review, we summarize our current knowledge on MCAM/MUC18 and IL-8, their transcriptional regulation, and their role in melanoma growth, angiogenesis and metastasis. Further, we report on the development of new fully human antibodies, anti-MCAM/MUC18 (ABX-MA1) and anti-IL-8 (ABX-IL8), and their effects on tumor growth and metastasis in animal models. Collectively, our studies suggest that ABX-MA1 and ABX-IL8 could serve as new modalities for the treatment of melanoma either alone, or in combination with conventional chemotherapy or other antitumor agents.
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PMID:Bioimmunotherapy for melanoma using fully human antibodies targeting MCAM/MUC18 and IL-8. 1696 68