Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study

Abstract

BackgroundThe main focus of several studies concerned with cancer progression and metastasis is to analyze the mechanisms that allow cancer cells to interact and quickly adapt with their environment. Integrins, a family of transmembrane glycoproteins, play a major role in invasive and metastatic processes. Integrins are involved in cell adhesion in both cell-extracellular matrix and cell-cell interactions, and particularly, β1 integrin is involved in proliferation and differentiation of cells in the development of epithelial tissues. This work aimed to investigate the putative role of β1 integrin expression on survival and metastasis in patients with breast invasive ductal carcinoma (IDC). In addition, we compared the expression of β1 integrin in patients with ductal carcinoma in situ (DCIS).MethodsThrough tissue microarray (TMA) slides containing 225 samples of IDC and 67 samples of DCIS, β1 integrin expression was related with several immunohistochemical markers and clinicopathologic features of prognostic significance.Resultsβ1 integrin was overexpressed in 32.8% of IDC. In IDC, β1 integrin was related with HER-2 (p = 0.019) and VEGF (p = 0.011) expression and it had a significant relationship with metastasis and death (p = 0.001 and p = 0.05, respectively). Kaplan-Meier survival analysis showed that the overexpression of this protein is very significant (p = 0.002) in specific survival (number of months between diagnosis and death caused by the disease). There were no correlation between IDC and DCIS (p = 0.559) regarding β1 integrin expression.ConclusionsConsidering that the expression of β1 integrin in breast cancer remains controversial, specially its relation with survival of patients, our findings provide further evidence that β1 integrin can be a marker of poor prognosis in breast cancer.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6652215267393871

A cell–ECM screening method to predict breast cancer metastasis

“…High β 1 expression is associated with poor prognosis, 48 and in our work, targeting β 1 integrin makes the MDA-MB-231 cell line much less bone tropic, matching this result (Fig. 4a).…”

“…When we compared our in vitro phenotyping approach to this existing gene data set, we found that our in vitro tropism responses imperfectly correlated with these genetic indicators. High b 1 expression is associated with poor prognosis, 48 and in our work, targeting b 1 integrin makes the MDA-MB-231 cell line much less bone tropic, matching this result (Fig. 4a).…”

A cell–ECM screening method to predict breast cancer metastasis

“…High β 1 expression is associated with poor prognosis, 48 and in our work, targeting β 1 integrin makes the MDA-MB-231 cell line much less bone tropic, matching this result (Fig. 4a).…”

“…When we compared our in vitro phenotyping approach to this existing gene data set, we found that our in vitro tropism responses imperfectly correlated with these genetic indicators. High b 1 expression is associated with poor prognosis, 48 and in our work, targeting b 1 integrin makes the MDA-MB-231 cell line much less bone tropic, matching this result (Fig. 4a).…”

13 1 ‐Oxophorbine protopheophorbide A from Ziziphus lotus as a novel mesenchymal‐epithelial transition factor receptor inhibitory lead for the control of breast tumor growth in vitro and in vivo

“…Based on the fact that tumor progression is associated with expression and activation of integrins such as αvβ3, β3, α5 and β1 and that these adhesion and growth factor receptors can induce signaling events that synergistically act to modulate cell functions including proliferation, protopheophorbide A inhibitory effect might be due in‐part to modulation of these integrins. In line with our results, it has been shown that blocking β1 integrin, the survival indicator in breast cancer decreased cell proliferation and induced apoptosis . Moreover, through receptor tyrosine kinases (RTKs), β1 coordinates its downstream signaling pathways including FAK, PI3K and ERK/MAPK involved in tumor initiation, progression and metastasis .…”

Identification and Functional Validation of RAD23B as a Potential Protein in Human Breast Cancer Progression

“…However, our comparative study yielded several differentially expressed proteins that were found to overlap with recent cell line studies on breast cancer invasion and metastasis, such as KRT8, ,, KRT19, VIM, HSPB1, ,, ITGB1, CD44, CapG, and CLIC1. ,, Other identified proteins, such as ANX7, AKR1B1, and FLNA, have been previously linked to playing a role in cancer.…”

A cell–ECM screening method to predict breast cancer metastasis

“…High β 1 expression is associated with poor prognosis, 48 and in our work, targeting β 1 integrin makes the MDA-MB-231 cell line much less bone tropic, matching this result (Fig. 4a).…”

“…When we compared our in vitro phenotyping approach to this existing gene data set, we found that our in vitro tropism responses imperfectly correlated with these genetic indicators. High b 1 expression is associated with poor prognosis, 48 and in our work, targeting b 1 integrin makes the MDA-MB-231 cell line much less bone tropic, matching this result (Fig. 4a).…”

13 1 ‐Oxophorbine protopheophorbide A from Ziziphus lotus as a novel mesenchymal‐epithelial transition factor receptor inhibitory lead for the control of breast tumor growth in vitro and in vivo

“…Based on the fact that tumor progression is associated with expression and activation of integrins such as αvβ3, β3, α5 and β1 and that these adhesion and growth factor receptors can induce signaling events that synergistically act to modulate cell functions including proliferation, protopheophorbide A inhibitory effect might be due in‐part to modulation of these integrins. In line with our results, it has been shown that blocking β1 integrin, the survival indicator in breast cancer decreased cell proliferation and induced apoptosis . Moreover, through receptor tyrosine kinases (RTKs), β1 coordinates its downstream signaling pathways including FAK, PI3K and ERK/MAPK involved in tumor initiation, progression and metastasis .…”

Identification and Functional Validation of RAD23B as a Potential Protein in Human Breast Cancer Progression

“…However, our comparative study yielded several differentially expressed proteins that were found to overlap with recent cell line studies on breast cancer invasion and metastasis, such as KRT8, ,, KRT19, VIM, HSPB1, ,, ITGB1, CD44, CapG, and CLIC1. ,, Other identified proteins, such as ANX7, AKR1B1, and FLNA, have been previously linked to playing a role in cancer.…”

A cell–ECM screening method to predict breast cancer metastasis

“…High β 1 expression is associated with poor prognosis, 48 and in our work, targeting β 1 integrin makes the MDA-MB-231 cell line much less bone tropic, matching this result (Fig. 4a).…”

“…When we compared our in vitro phenotyping approach to this existing gene data set, we found that our in vitro tropism responses imperfectly correlated with these genetic indicators. High b 1 expression is associated with poor prognosis, 48 and in our work, targeting b 1 integrin makes the MDA-MB-231 cell line much less bone tropic, matching this result (Fig. 4a).…”

13 1 ‐Oxophorbine protopheophorbide A from Ziziphus lotus as a novel mesenchymal‐epithelial transition factor receptor inhibitory lead for the control of breast tumor growth in vitro and in vivo

“…Based on the fact that tumor progression is associated with expression and activation of integrins such as αvβ3, β3, α5 and β1 and that these adhesion and growth factor receptors can induce signaling events that synergistically act to modulate cell functions including proliferation, protopheophorbide A inhibitory effect might be due in‐part to modulation of these integrins. In line with our results, it has been shown that blocking β1 integrin, the survival indicator in breast cancer decreased cell proliferation and induced apoptosis . Moreover, through receptor tyrosine kinases (RTKs), β1 coordinates its downstream signaling pathways including FAK, PI3K and ERK/MAPK involved in tumor initiation, progression and metastasis .…”

Identification and Functional Validation of RAD23B as a Potential Protein in Human Breast Cancer Progression

“…However, our comparative study yielded several differentially expressed proteins that were found to overlap with recent cell line studies on breast cancer invasion and metastasis, such as KRT8, ,, KRT19, VIM, HSPB1, ,, ITGB1, CD44, CapG, and CLIC1. ,, Other identified proteins, such as ANX7, AKR1B1, and FLNA, have been previously linked to playing a role in cancer.…”