Expression of the neuroglandular antigen and analogues in melanoma. CD9 expression appears inversely related to metastatic potential of melanoma

Abstract

Immunohistological methods were used to examine the relation between the metastatic potential of melanoma and expression of the neuroglandular antigen (CD63) and other members of this family of molecules, CD53, CD37, CD9 and the target of an anti-proliferative antibody (TAPA-I), as well as MHC-class-I and -II antigens. The criteria used to establish metastatic potential were their relation to thickness of the primary melanoma, and differences in expression between vertical and radial growth phases of primary melanoma and between primary and metastatic melanoma. Studies on basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) were also included as controls for malignant skin cancers with low metastatic potential. Expression of CD9 and MHC-class-I antigen was found to be inversely related to thickness of the primary tumor, and CD9 was expressed predominantly on primary rather than on metastatic tumors. CD9 expression correlated with MHC-class-I expression on melanoma, and both were expressed on BCCs and SCCs having low metastatic potential, but not on compound nevi. CD63 and TAPA-I were expressed on nevi but not on SCC and BCC. Leu 13 is a molecule associated with TAPA-I in lymphomas, and was found to be expressed in sections from 5 out of 34 primary and 5 out of 21 metastatic melanoma. CD53 and CD37 were not detected on melanoma. Our results indicate that several members of the neuroglandular antigen are expressed in melanoma and that low expression of CD9 on primary melanomas might have prognostic significance with respect to the potential for metastasis.

EpCAM (CD326) finding its role in cancer

“…One of them, CD9, was shown by crosslinking experiments to directly bind EpCAM whereas other proteins including ADAM10, integrins, G proteins, and a novel CD9 binding protein (CD9P-1) were indirectly associated. Intriguingly, loss of CD9 expression correlates with metastasis (Si and Hersey, 1993;Miyake et al, 1996;Zheng et al, 2005) and, as reported at the symposium, a strict co-localisation of CD9 and EpCAM, as seen for membranes of normal colonic epithelium, was no longer found for tumour cell membranes.…”

Therapeutic Window of MuS110, a Single-Chain Antibody Construct Bispecific for Murine EpCAM and Murine CD3

“…Upon neoplastic transformation, EpCAM can be overexpressed on certain tumor cells, which may titrate out protein partners. Likewise, free EpCAM may arise from loss of protein partners during transformation, as has been reported for CD9 (45). Accessibility of EpCAM-expressing cells to both antibodies and immune effector cells may further increase upon degradation of extracellular matrix by tumor cellderived proteases and by loss of tight junctions in tumor tissue.…”

A decrease in the expression of CD63 tetraspanin protein elevates invasive potential of human melanoma cells

“…Among these molecules, CD9 plays a role in inhibiting melanoma metastasis since its expression induced by transfection or viral delivery of CD9 gene was found to suppress motility and metastasis of mouse melanoma cells (Ikeyama et al, 1993;Miyake et al, 2000). CD9 expression has also been inversely related to metastatic potential of melanoma (Si and Hersey, 1993). It thus appears that melanoma metastasis is not inhibited only by CD63, but also by CD9.…”

“…The tetraspanin molecules have been implicated in diverse biological phenomena, including cell proliferation, activation, adhesion, migration, differentiation, and development. Some of these molecules have also been implicated in cancer metastasis: CD9 expression is inversely correlated with the appearance of metastases in melanomas, breast, lung, and colon cancers (Si and Hersey, 1993;Miyake et al, 1995;Adachi et al, 1998;Mori et al, 1998). CD82, which was rediscovered as the KAI1 metastasis-suppressor gene product, also become down-regulated in the malignant progression of many types of human cancers, including prostate, breast, pancreatic, lung, bladder, and gastric cancer (Guo et al, 1996;Ueda et al, 1996;Yang et al, 1997;Yu et al, 1997;Higashiyama et al, 1998;Hinoda et al, 1998).…”