title: IgG1-iS18 impedes the adhesive and invasive potential of early and late stage malignant melanoma cells.
abstract: The 37kDa/67kDa laminin receptor (LRP/LR) is a non-integrin laminin receptor which is overexpressed in tumorigenic cells and supports progression of cancer via promoting metastasis, angiogenesis and telomerase activity and impediment of apoptosis. The present study investigates the role of LRP/LR on the metastatic potential of early (A375) and late (A375SM) stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. Flow cytometry and western blot analysis showed that late stage malignant melanoma cells display significantly higher total and cell surface LRP/LR levels in comparison to early stage malignant melanoma cells and the poorly invasive breast cancer (MCF-7) control cell line. Targeting LRP/LR using the LRP/LR specific antibody IgG1-iS18 resulted in a significant reduction of the adhesive potential to laminin-1 and the invasive potential through the 'ECM-simulating' Matrigel™ of both early and late stage malignant melanoma cells. Furthermore, Pearson's correlation coefficient confirmed that increased LRP levels correlate with the increased invasive and adhesive potential in early and late stage melanoma cells. Thus, blocking LRP/LR using the IgG1-iS18 antibody may therefore be a promising therapeutic strategy for early and late stage malignant melanoma treatment.
authors.affiliation: From the School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: 727874@students.wits.ac.za.
authors.forename: Carmelle
authors.initials: C
authors.lastname: Munien
authors.affiliation: From the School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: 600344@students.wits.ac.za.
authors.forename: Thalia M
authors.initials: TM
authors.lastname: Rebelo
authors.affiliation: From the School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: eloise.vandermerwe@wits.ac.za.
authors.forename: Eloise
authors.initials: E
authors.lastname: Ferreira
authors.affiliation: From the School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: stefan.weiss@wits.ac.za.
authors.forename: Stefan F T
authors.initials: SF
authors.lastname: Weiss
mesh_terms: D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007797:Laminin / Q000737:chemistry; D061986:MCF-7 Cells; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009367:Neoplasm Staging; D011509:Proteoglycans / Q000737:chemistry; D017474:Receptors, Laminin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000912:Antibodies, Neoplasm; D057134:Antibodies, Neutralizing; D004338:Drug Combinations; D007074:Immunoglobulin G; D007797:Laminin; D011509:Proteoglycans; D017474:Receptors, Laminin; C121346:laminin 1; C059485:matrigel; D003094:Collagen
keywords: 37kDa/67kDa laminin receptor (LRP/LR); Adhesion; Invasion; Laminin-1; Melanoma, IgG1-iS18 antibody