Integrin α11β1 is expressed in breast cancer stroma and associates with aggressive tumor phenotypes

Cancer-associated fibroblasts are essential modifiers of the tumor microenvironment. The collagen-binding integrin alpha11beta1 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 alpha11beta1 in a large breast cancer series using a novel antibody against the human integrin alpha11 chain. Several novel monoclonal antibodies against the integrin alpha11 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 alpha11 in relation to alphaSMA and cytokeratin-14 were also investigated. Integrin alpha11 was expressed to varying degrees in spindle-shaped cells in the stroma of 99% of invasive breast carcinomas. Integrin alpha11 co-localized with alphaSMA in stromal cells, and with alphaSMA and cytokeratin-14 in breast myoepithelium. High stromal integrin alpha11 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 alpha11 expression was associated with aggressive breast cancer phenotypes.