ADAM10 Is Upregulated in Melanoma Metastasis Compared with Primary Melanoma

Abstract

ADAM10 (a disintegrin and metalloproteinase 10) is involved in the ectodomain shedding of various substrates, including adhesion molecules such as L1 cell adhesion molecule (L1-CAM) and CD44, which are known to have important roles in the development of malignant melanoma. In our study, we characterized the expression of ADAM10 in melanoma cells in vitro and in vivo. Immunohistochemical analysis on tissue microarrays indicated that ADAM10 expression was significantly elevated in melanoma metastasis compared with primary melanomas. In vitro downregulation of ADAM10 with specific small interfering RNA (siRNA) resulted in a suppression of the anchorage-independent cell growth and reduced the migration of melanoma cells. In addition, overexpression of ADAM10 induced the migration of melanoma cells. In cell lines from melanoma patients with metastasis, ADAM10 was significantly overexpressed, and ADAM10 expression correlated with increased cell proliferation. Furthermore, we present evidence that ADAM10 is involved in the release of L1-CAM from melanoma cells. It is important that knockdown of cellular L1-CAM reduced the migration of melanoma cells and abrogated the chemoresistance against cisplatin. In contrast, soluble L1-CAM had no effect on melanoma cell migration or cell survival. Taken together, our data demonstrate that ADAM10 and L1-CAM have important roles during melanoma progression and both molecules represent attractive targets for therapeutical intervention of melanomas.

Multi-omics Analysis of Serum Samples Demonstrates Reprogramming of Organ Functions Via Systemic Calcium Mobilization and Platelet Activation in Metastatic Melanoma

“…S3) have already been identified by us in the secretome of mesenchymal cells in the context of tumorassociated inflammation (55). CD44 shedding has directly been linked to calcium mobilization and contributes to metastasis (56). The interrelation between inflammation, calcium, reactive oxygen species and specific stress signatures like endoplasmic reticulum stress is well established (57).…”

A disintegrin and metalloprotease (ADAM)10 is highly expressed in hepatocellular carcinoma and is associated with tumour progression

“…24,25 Among them, ADAM10 is known to be involved in tumour progression. 11,12,16,17,26 It has been reported that ADAM10 can cleave collagen type IV in the basement membrane, which is relevant to tumour metastasis. 11 Murai et al showed that the cleavage of CD44 catalyzed by ADAM10 contributed to the migration and invasion of glioblastoma tumour cells.…”

Clinical significance of ADAM10 expression in laryngeal carcinoma

“…A number of ADAMs, including ADAM9, ADAM10, ADAM12 and ADAM17, are critical during the genesis, development and metastasis of cancers (21,25,26). Dysregulated expression of ADAM10 has been reported in various malignancies, and has been suggested to be involved in cancer progression (10)(11)(12)(13)(14)(15)(16)(17).…”

“…Thus, ADAM family members, including ADAM10, serve pivotal roles in the pathogenesis or progression of cancers, including proliferation, angiogenesis, migration and invasion (6)(7)(8)(9). Analysis of gene expression profiles revealed that the ADAM10 gene was significantly overexpressed in a wide variety of human malignancies, including hepatocellular carcinoma, melanoma, oral squamous cell carcinoma, lung cancer, pancreatic carcinoma, and gastric and bladder cancer (10)(11)(12)(13)(14)(15)(16)(17). Accumulating evidence has illustrated that ADAM10 contributed to the regulation of cancer progression, chemoresistance and metastasis via the cleavage of growth factors or cell surface proteins (6,8,10,12,(18)(19)(20)(21).…”

“…Analysis of gene expression profiles revealed that the ADAM10 gene was significantly overexpressed in a wide variety of human malignancies, including hepatocellular carcinoma, melanoma, oral squamous cell carcinoma, lung cancer, pancreatic carcinoma, and gastric and bladder cancer (10)(11)(12)(13)(14)(15)(16)(17). Accumulating evidence has illustrated that ADAM10 contributed to the regulation of cancer progression, chemoresistance and metastasis via the cleavage of growth factors or cell surface proteins (6,8,10,12,(18)(19)(20)(21). Recently, it was reported that ADAM10 is overexpressed in hepatocellular carcinoma tissues, and that there are significant associations between ADAM10 expression levels and tumor grade, tumor differentiation, tumor size and metastasis (10).…”