ABSTRACT
Cancer-associated fibroblasts are essential modifiers of the tumor microenvironment. The collagen-binding integrin α11ß1 has been proposed to be upregulated in a pro-tumorigenic subtype of cancer-associated fibroblasts. Here, we analyzed the expression and clinical relevance of integrin α11ß1 in a large breast cancer series using a novel antibody against the human integrin α11 chain. Several novel monoclonal antibodies against the integrin α11 subunit were tested for use on formalin-fixed paraffin-embedded tissues, and Ab 210F4B6A4 was eventually selected to investigate the immunohistochemical expression in 392 breast cancers using whole sections. mRNA data from METABRIC and co-expression patterns of integrin α11 in relation to αSMA and cytokeratin-14 were also investigated. Integrin α11 was expressed to varying degrees in spindle-shaped cells in the stroma of 99% of invasive breast carcinomas. Integrin α11 co-localized with αSMA in stromal cells, and with αSMA and cytokeratin-14 in breast myoepithelium. High stromal integrin α11 expression (66% of cases) was associated with aggressive breast cancer features such as high histologic grade, increased tumor cell proliferation, ER negativity, HER2 positivity, and triple-negative phenotype, but was not associated with breast cancer specific survival at protein or mRNA levels. In conclusion, high stromal integrin α11 expression was associated with aggressive breast cancer phenotypes.
Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma/metabolism , Integrin alpha Chains/biosynthesis , Aged , Antibodies, Monoclonal , Carcinoma/pathology , Female , Humans , Integrin alpha Chains/analysis , Integrins/analysis , Integrins/biosynthesis , Middle Aged , Phenotype , Receptors, Collagen/analysis , Receptors, Collagen/biosynthesisABSTRACT
Well-understood functions for "traditional" platelet receptors are described, but "newer" receptors are equally discussed. Receptors are described biochemically (structure, ligand(s), protein partners, and function) and whenever possible, their clinical importance (mutations, polymorphisms, syndrome) are highlighted.
Subject(s)
Blood Platelets/chemistry , Receptors, Cell Surface/analysis , Animals , Humans , Integrins/analysis , Platelet Adhesiveness , Platelet Aggregation , Platelet Glycoprotein GPIb-IX Complex/analysis , Receptors, Cell Surface/physiology , Receptors, Collagen/analysis , Receptors, Prostaglandin E/analysisABSTRACT
Collagen peptides have been used to identify binding sites for several important collagen receptors, including integrin alpha(2)beta(1), glycoprotein VI, and von Willebrand factor. In parallel, the structures of these collagen receptors have been reported, and their interactions with collagen peptides have been studied. Recently, the three-dimensional structure of the intact type I collagen fiber from rat tail tendon has been resolved by fiber diffraction. It is now possible to map the binding sites of platelet collagen receptors onto the intact collagen fiber in three dimensions. This minireview will discuss these recent findings and their implications for platelet activation by collagen.
