The α₂β₁ integrin is a metastasis suppressor in mouse models and human cancer.
Integrins regulate cell-cell and cell-matrix adhesion and thereby play critical roles in tumor progression and metastasis. Although work in preclinical models suggests that β1 integrins may stimulate metastasis of a number of cancers, expression of the β1 subunit alone has not been shown to be a useful prognostic indicator in human cancer patients. Here we have demonstrated that the α2β1 integrin suppresses metastasis in a clinically relevant spontaneous mouse model of breast cancer. These data are consistent with previous studies indicating high expression of α2β1 integrin in normal breast epithelium and loss of α2β1 in poorly differentiated breast cancer. They are also consistent with our systematic analysis of microarray databases of human breast and prostate cancer, which revealed that decreased expression of the gene encoding α2 integrin, but not genes encoding α1, α3, or β1 integrin, was predictive of metastatic dissemination and decreased survival. The predictive value of α2 expression persisted within both good-risk and poor-risk cohorts defined by estrogen receptor and lymph node status. Thus, the α2β1 integrin functionally inhibits breast tumor metastasis, and α2 expression may serve as an important biomarker of metastatic potential and patient survival.
Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2561, USA.
Norma E
NE
Ramirez
Zhonghua
Z
Zhang
Aasakiran
A
Madamanchi
Kelli L
KL
Boyd
Lynda D
LD
O'Rear
Abudi
A
Nashabi
Zhengzi
Z
Li
William D
WD
Dupont
Andries
A
Zijlstra
Mary M
MM
Zutter
D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D066298:In Vitro Techniques; D038982:Integrin alpha2beta1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D014408:Biomarkers, Tumor; D017931:DNA Primers; D038982:Integrin alpha2beta1; D025521:Tumor Suppressor Proteins