Supplementary Tables S1-S4 from MMP16 Mediates a Proteolytic Switch to Promote Cell–Cell Adhesion, Collagen Alignment, and Lymphatic Invasion in Melanoma

Tatti, Olga; Gucciardo, Erika; Pekkonen, Pirita; Holopainen, Tanja; Louhimo, Riku; Repo, Pauliina; Maliniemi, Pilvi; Lohi, Jouko; Rantanen, Ville; Hautaniemi, Sampsa; Alitalo, Kari; Ranki, Annamari; Ojala, Päivi M.; Keski-Oja, Jorma; Lehti, Kaisa

doi:10.1158/0008-5472.22404674.v1

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Supplementary Tables S1-S4 from MMP16 Mediates a Proteolytic Switch to Promote Cell–Cell Adhesion, Collagen Alignment, and Lymphatic Invasion in Melanoma

journal contribution

posted on 2023-03-30, 23:00 authored by Olga Tatti, Erika Gucciardo, Pirita Pekkonen, Tanja Holopainen, Riku Louhimo, Pauliina Repo, Pilvi Maliniemi, Jouko Lohi, Ville Rantanen, Sampsa Hautaniemi, Kari Alitalo, Annamari Ranki, Päivi M. Ojala, Jorma Keski-Oja, Kaisa Lehti

Supplementary Tables S1-S4. MMPs which are significantly over-expressed in melanoma cell lines compared to the mean expression of all cancer cell lines in the datasets with over 15 melanoma cell lines (S1); Outlier analysis of MMP16 copy number gain or over-expression using DNA and mRNA datasets containing more than 20 clinical melanoma samples (S2); MMP mRNA expression, LVI and clinicopathological data of human melanoma tumors (S3); S100B staining coverage, lymphatic and blood vessel densities of human melanoma tumors (S4)

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ARTICLE ABSTRACT

Lymphatic invasion and accumulation of continuous collagen bundles around tumor cells are associated with poor melanoma prognosis, but the underlying mechanisms and molecular determinants have remained unclear. We show here that a copy-number gain or overexpression of the membrane-type matrix metalloproteinase MMP16 (MT3-MMP) is associated with poor clinical outcome, collagen bundle assembly around tumor cell nests, and lymphatic invasion. In cultured WM852 melanoma cells derived from human melanoma metastasis, silencing of MMP16 resulted in cell-surface accumulation of the MMP16 substrate MMP14 (MT1-MMP) as well as L1CAM cell adhesion molecule, identified here as a novel MMP16 substrate. When limiting the activities of these trans-membrane protein substrates toward pericellular collagen degradation, cell junction disassembly, and blood endothelial transmigration, MMP16 supported nodular-type growth of adhesive collagen-surrounded melanoma cell nests, coincidentally steering cell collectives into lymphatic vessels. These results uncover a novel mechanism in melanoma pathogenesis, whereby restricted collagen infiltration and limited mesenchymal invasion are unexpectedly associated with the properties of the most aggressive tumors, revealing MMP16 as a putative indicator of adverse melanoma prognosis. Cancer Res; 75(10); 2083–94. ©2015 AACR.