Dual Roles of the Melanoma CAM (MelCAM/METCAM) in Malignant Progression of Melanoma

Wu, Guang-Jer

doi:10.5772/22529

Cited by 3 publications

(13 citation statements)

References 40 publications

(78 reference statements)

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“…The conclusion, nevertheless, appears to be consistent with the first notion suggested by one group that METCAM/MUC18 is a tumor suppressor in human breast cancer cell line MCF-7 [ 28 ]; albeit the notion was later proven to contradict to the evidence from two different groups [ 23 , 24 , 27 ]. Regardless, the role of METCAM/MUC18 as a tumor suppressor was not only conclusively demonstrated in a human ovarian cancer cell line, SK-OV-3 (as shown here), but also in another human ovarian cancer cell line BG-1 [Wu, unpublished results], as well as in a mouse melanoma cell line, K1735-9 [ 34 ] and one NPC cell line, NPC-TW01 ([ 35 , 36 ], & Wu, unpublished results). METCAM/MUC18 has also been demonstrated as a metastasis suppressor in the two human ovarian cancer cell lines, SK-OV-3 (as also shown here) and BG-1 [Wu, unpublished results], and one mouse melanoma cell line, K1735-9 [ 34 ].…”

Section: Discussionmentioning

confidence: 61%

“…Regardless, the role of METCAM/MUC18 as a tumor suppressor was not only conclusively demonstrated in a human ovarian cancer cell line, SK-OV-3 (as shown here), but also in another human ovarian cancer cell line BG-1 [Wu, unpublished results], as well as in a mouse melanoma cell line, K1735-9 [ 34 ] and one NPC cell line, NPC-TW01 ([ 35 , 36 ], & Wu, unpublished results). METCAM/MUC18 has also been demonstrated as a metastasis suppressor in the two human ovarian cancer cell lines, SK-OV-3 (as also shown here) and BG-1 [Wu, unpublished results], and one mouse melanoma cell line, K1735-9 [ 34 ]. Thus sufficient evidence is provided to support the novel suppressor role of METCAM/MCU18 in the progression of these human cancers.…”

Section: Discussionmentioning

confidence: 61%

“…Thus the most intriguing, unique biological function of METCAM/MUC18 in tumorigenesis and metastasis is that it seems to play a dual role in the progression of some tumor cell lines. It can be a tumor/metastasis promoter in prostate cancer cell lines [ 22 , 26 ], breast cancer cell lines [ 23 , 24 , 27 ], and most melanoma cell lines [ 19 , 25 , 34 ]. It can also be a tumor/metastasis suppressor in the progression of other tumor cell lines in animal studies, such as, two ovarian cancer cell lines (in this report and Wu, unpublished results), one mouse melanoma subline ([ 34 ] and Wu, unpublished results), nasopharyngeal carcinoma ([ 35 , 36 ] and Wu, unpublished results), and perhaps hemangioma [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

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METCAM/MUC18 is a novel tumor and metastasis suppressor for the human ovarian cancer SKOV3 cells

Zeng

2016

BMC Cancer

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BackgroundIncreased expression of METCAM/MUC18, a trans-membrane cell adhesion molecule in the Ig-like gene superfamily, has been associated with the malignant progression of epithelial ovarian carcinomas. To investigate if this is a fortuitous correlation or if METCAM/MUC18 actually plays a role in the progression of the cancer, we tested effects of enforced expression of METCAM/MUC18 on in vitro behaviors, in vivo tumorigenesis, and in vivo malignant progression of human ovarian cancer SK-OV-3 cells, which minimally expressed this protein.MethodsFor in vitro and in vivo tests, we transfected human METCAM/MUC18 cDNA gene into SK-OV-3 cells in a mammalian expression vector pcDNA3.1+ and obtained G418-resistant (G418R) clones, which expressed various levels of human METCAM/MUC18. To mimic physiological situations, we used pooled METCAM/MUC18-expressing and control (vector) clones for testing effects of human METCAM/MUC18 over-expression on in vitro motility and invasiveness, and on in vivo tumor formation and metastasis in female athymic nude mice. Effects of METCAM/MUC18 on the expression of various downstream key factors related to tumorigenesis were also evaluated by Western blot analyses.ResultsThe over-expression of METCAM/MUC18 inhibited in vitro motility and invasiveness of SK-OV-3 cells. SK-OV-3 cells of the control (vector) clone (3D), which did not express human METCAM/MUC18, supported the formation of a solid tumor after SC injection of the cells at dorsal or ventral sites and also formation of solid tumor and ascites after IP injection in the intraperitoneal cavity of nude mice. In contrast, SK-OV-3 cells from the METCAM/MUC18-expressing clone (2D), which expressed a high level of METCAM/MUC18, did not support the formation of a solid tumor at SC sites, or formation of ascites in the intraperitoneal cavity of nude mice. Expression levels of downstream key factors, which may affect tumor proliferation and angiogenesis, were reduced in tumors induced by the METCAM/MUC18-expressing clone (2D).ConclusionsWe conclude that increased human METCAM/MUC18 expression in ovarian cancer SK-OV-3 cells suppressed tumorigenesis and ascites formation in nude mice, suggesting that human METCAM/MUC18 plays a suppressor role in the progression of ovarian cancer, perhaps by reducing proliferation and angiogenesis.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

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METCAM/MUC18 is a novel tumor and metastasis suppressor for the human ovarian cancer SKOV3 cells

Zeng

2016

BMC Cancer

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“…HuMETCAM/MUC18 may mediate hematogenous spreading of melanoma cells, as implicated by its expression in endothelial cells and malignant melanoma cells [106] and presence in junctions of endothelial cells [107,108], essential for tumor angiogenesis in three tumor cell lines [109] and human prostate cancer LNCaP cells [110], and it is highly likely for that in other cancers [111,112]. HuMETCAM/MUC18 may also be implicated in promoting lymphatic metastasis of cancer cells, since it is one of the lymphatic metastasis-associated genes, which are upregulated in malignant mouse hepatocellular carcinoma [113].…”

Section: Signaling Pathwaysmentioning

confidence: 99%

“…Different intrinsic cofactors in different cancer cell lines may modulate METCAM/MUC18 and alter cell-to-cell and cell-extracellular matrix interactions in the tumor microenvironment, resulting in affecting tumor progression and metastasis in vivo. Finally, these cofactors/ligands may interact differently with METCAM/MUC18 in different cell lines and affect other host physiological factors, which may augment or suppress in vivo tumor progression and metastasis by affecting metabolic switch, pro-apoptosis/anti-apoptosis, tumor angiogenesis, and host immune system in the tumor micro-milieu and in various metastatic sites [17,37,40,111,112]. Thus, the identification of the cofactors and the huMETCAM/MUC18cognate heterophilic ligand(s) is critical for understanding the mechanism.…”

Section: Heterophilic Ligands and Cofactors That Modulate The Functiomentioning

confidence: 99%

METCAM/MUC18 Promotes Tumor Progression and Metastasis in Most Human Cancers

Wu¹

2020

Tumor Progression and Metastasis

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In addition to oncogenes and tumor suppressor genes, cell adhesion molecules (CAMs) also significantly contribute to tumor progression and metastasis. For the past two decades, we have demonstrated that METCAM/MUC18, a cell adhesion molecule in the immunoglobulin-like gene superfamily, orchestrates complex interactions of tumor cells with various stromal cells in the tumor microenvironment, resulting in augmentation or reduction of the metastatic potential of carcinoma cells. Here we show that METCAM/MUC18 plays a positive role in the tumor progression and metastasis in most human cancers, such as breast cancer, human melanoma and most mouse melanoma, nasopharyngeal carcinoma type III, prostate cancer LNCaP and DU145 cell lines, and perhaps angiosarcoma, gastric cancer, glioma, hepatocellular carcinoma, non-small cell lung adenocarcinoma, small cell lung cancer (SCLC), osteosarcoma, and human and mouse pancreatic cancer. Possible mechanisms in the METCAM/MUC18-mediated tumor progression and metastasis are proposed. Anti-METCAM/MUC18 antibodies and siRNAs may be used as therapeutic agents to treat these cancers.

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METCAM/MUC18 Decreases the Malignant Propensity of Human Ovarian Carcinoma Cells

2018

IJMS

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METCAM/MUC18 is an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family. It can carry out common functions of CAMs which is to perform intercellular interactions and interaction of cell with extracellular matrix in tumor microenvironment, to interact with various signaling pathways and to regulate general behaviors of cells. We and other two groups previously suggested that METCAM/MUC18 probably be utilized as a biomarker for predicting the malignant tendency of clinical ovarian carcinomas, since METAM/MUC18 expression appears to associate with the carcinoma at advanced stages. It has been further postulated to promote the malignant tendency of the carcinoma. However, our recent research results appear to support the conclusion that the above positive correlation is fortuitous; actually METCAM/MUC18 acts as a tumor and metastasis suppressor for the ovarian carcinoma cells. We also suggest possible mechanisms in the METCAM/MUC18-mediated early tumor development and metastasis of ovarian carcinoma. Moreover, we propose to employ recombinant METCAM/MUC18 proteins and other derived products as therapeutic agents to treat the ovarian cancer patients by decreasing the malignant potential of ovarian carcinoma.

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Dual Roles of the Melanoma CAM (MelCAM/METCAM) in Malignant Progression of Melanoma

Cited by 3 publications

References 40 publications

METCAM/MUC18 is a novel tumor and metastasis suppressor for the human ovarian cancer SKOV3 cells

METCAM/MUC18 is a novel tumor and metastasis suppressor for the human ovarian cancer SKOV3 cells

METCAM/MUC18 Promotes Tumor Progression and Metastasis in Most Human Cancers

METCAM/MUC18 Decreases the Malignant Propensity of Human Ovarian Carcinoma Cells

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