Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146)

Taichi Ishikawa, Zenebech Wondimu, Yuko Oikawa, Giusy Gentilcore, Rolf Kiessling, Suzanne Egyhazi Brage, Johan Hansson, Manuel Patarroyo

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Abstract

α4-laminins, such as laminins 411 and 421, are mesenchymal laminins expressed by blood and lymphatic vessels and some tumor cells. Laminin-411 promotes migration of leukocytes and endothelial cells, but the effect of this laminin and laminin-421 on tumor cells is poorly understood. In the present study, we demonstrate that laminin-411 and, to a greater extent, laminin-421 significantly promote migration of tumor cells originated from melanomas, gliomas and different carcinomas via α6β1 integrin. In solid-phase binding assays, both laminins similarly bound α6β1 integrin but only laminin-421, among several laminin isoforms, readily bound MCAM (CD146), a cell-surface adhesion molecule strongly associated with tumor progression. Accordingly, a function-blocking mAb to MCAM inhibited tumor cell migration on laminin-421 but not on laminins 411 or 521. In tumor tissues, melanoma cells co-expressed MCAM, laminin α4, β1, β2 and γ1 chains, and integrin α6 and β1 chains. The present data highlight the novel role of α4-laminins in tumor cell migration and identify laminin-421 as a primary ligand for MCAM and a putative mediator of tumor invasion and metastasis.

Original languageEnglish
Pages (from-to)69-83
Number of pages15
JournalMatrix Biology
Volume38
DOIs
Publication statusPublished - 1 Sep 2014

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Keywords

  • CD146
  • Cell migration
  • Integrin
  • Laminin
  • MCAM

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Ishikawa, T., Wondimu, Z., Oikawa, Y., Gentilcore, G., Kiessling, R., Egyhazi Brage, S., Hansson, J., & Patarroyo, M. (2014). Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146). Matrix Biology, 38, 69-83. https://doi.org/10.1016/j.matbio.2014.06.002