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

Abstract

Cancer‐associated fibroblasts are essential modifiers of the tumor microenvironment. The collagen‐binding integrin α11β1 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 α11β1 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.

Reciprocal Interplay Between Fibrillar Collagens and Collagen-Binding Integrins: Implications in Cancer Progression and Metastasis

“…Our study revealed that high stromal integrin α11/PDGFRβ expression is correlated with a poorer clinical outcome in breast cancer patients and that this integrin harnesses the PDGFRβ/JNK signaling pathway to promote the invasion of cancer cells (280). The implication of stromal α11β1 integrin in breast cancer was further investigated in another recent study, which emphasized the correlation of this integrin expression with aggressive phenotypes of breast cancer (334). Furthermore, an additional report highlighted the contribution of integrin α11 to breast cancer progression by regulating the intratumoral interstitial fluid pressure and collagen structure (335).…”

Expression of cornulin in tongue squamous cell carcinoma

“…The scoring assessment was based on the semi-quantitative immunoreactive score (IRS) by multiplying the positive intensity and the immunopositive cell percentage to obtain an IRS ranging from 0 to +9 [ 19 , 20 ]. The positive intensity scores were quantified using the following scores: negative = 0, weak = 1, moderate = 2 and strong = 3.…”

“…Protein expression of COL1A2, CRNN and DCN was classified into two groups; Low (IRS ≤ +3) and High (IRS ≥ +4), respectively. There is no pre-established cut-off value for COL1A2, CRNN and DCN so the frequency histograms for IRS were evaluated based on earlier studies [ 19 ] ( Supplementary Figure S1A–C , respectively).…”

Correlation between the features of β1 and β3 integrin expression and lymphangitic metastatic spread in nonspecific invasive breast carcinoma based on tumor morphological heterogeneity

“…Интегрины, участвующие в связывании клеток с коллагеном или ламинином, объединяют в другое подсемейство, которое включает β1 (α1β1, α2β1, α10β1, α11β1, α6β1) или β4 (α6β4) [1]. В этих взаимосвязях интегрины осуществляют двунаправленную коммуникацию между клетками и структурами внеклеточного матрикса [3].…”

“…Мало что известно о вкладе отдельных димеров интегрина в развитие тканевых и клеточных структур молочной железы, при этом отмечен тесный синергизм сигнальных путей интегринов и EGFR (Epidermal growth factor receptor) [1,2,4]. При инвазивной карциноме молочной железы повышенная экспрессия интегрина β1 в опухоли коррелирует с плохой выживаемостью, что де- монстрирует его вклад в формирование более злокачественного потенциала в клетках новообразования [3]. Показано, что ремоделирование микроокружения с повышением жесткости фибриллярных коллагенов под действием лизилоксидазы, а также повышение содержания β1 интегрина при РМЖ коррелируют с возникновением процессов злокачественной трансформации нормальной ткани в инвазивную карциному, определяя худший общий прогноз [5].…”