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

Abstract

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.

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

“…When the other human ovarian cancer cell line, BG-1, was similarly tested, similar results were also observed [80]. In summary, we supplied in vitro and in vivo evidence to definitely support the conclusion that METCAM/ MUC18 plays a suppressor role in the tumorigenesis and malignant progression of two human ovarian cancer cell lines [28][29][30]80], suggesting that METCAM/MUC18 is a strong candidate as a new tumor and metastasis suppressor in human ovarian cancer cells.…”

“…Moreover, METCAM/MUC18 may affect cancer cell progression by cross talk with signaling pathways that affect apoptosis, survival and proliferation, angiogenesis, and energy metabolism of tumor cells [6,8,101]. This is indeed found in our preliminary mechanical studies in breast cancer [19,20], melanoma [21,22], NPC [24][25][26], ovarian cancer [28][29][30], and prostate cancer [34][35][36][37]. Further systematic studies by using specific RNAi's to knockdown the downstream effectors one by one in the METCAM/MUC18-expressing clones may be necessary to further understand this aspect of mechanism.…”

“…In summary, METCAM/MUC18 may also suppress tumor progression and metastasis of the following solid tumors, such as colorectal cancer [77], mouse melanoma K1735-9 subline [22], NPC type I [24,25], ovarian cancer [28][29][30], human pancreatic cancer [81], one prostate cancer cell line PC-3 [82], and perhaps hemangioma [46]. Thus, METCAM/MUC18 appears to play a negative role in tumor progression and metastasis of some solid tumors but a dual role in some other solid tumors.…”

“…Since the huMETCAM/MUC18 was first discovered in the 1980s, three groups have worked on the role of huMETCAM/MUC18 in melanoma metastasis [38,39,55,56], another group on the role of huMETCAM/MUC18 in the biology of endothelial cells [41,83], and one group on breast cancer [45], and our group joined in the effort to study the role of huMETCAM/MUC18 in the progression of mouse melanoma [43] and prostate cancer [31][32][33][34][35][36] and later breast cancer [18][19][20], ovarian cancer [27][28][29][30], and NPC [23][24][25][26], as described above. Recently, more research groups have participated in further exploring the possible role of METCAM/MUC18 in other solid tumors in different organs, such as the colorectum [77], gastro-organ [60], glial cells [61], liver [63,64], lung [65][66][67][68][69][70][71], bone [72][73][74], and pancreas [75,76,81].…”

METCAM/MUC18: A Novel Tumor Suppressor for Some Cancers

“…Effects of the aberrant expression of the following CAMs on tumorigenesis and malignant progression are better studied, such as cadherin [9], integrins [10], CD44 [11], CEACAM [12], mucins [13], L1CAM [14], EpCAM [15], ALCAM [16] and METCAM/MUC18 [17]. Over the past several years, our team investigated the role of METCAM/MUC18 in several types of tumors, such as melanoma, breast, nasopharyngeal, ovarian and prostate cancers [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. The resulting data showed a dual role of METCAM/MUC18 as a tumor promotor or suppressor in these cancers [17,37].…”