Biphasic α2β1 Integrin Expression in Breast Cancer Metastasis to Bone

Integrins participate in the pathogenesis and progression of tumors at many stages during the metastatic cascade. However, current evidence for the role of integrins in breast cancer progression is contradictory and seems to be dependent on tumor stage, differentiation status, and microenvironmental...

Full description

Saved in:

Bibliographic Details
Published in:	International journal of molecular sciences Vol. 22; no. 13; p. 6906
Main Authors:	Moritz, Milene N O, Merkel, Alyssa R, Feldman, Ean G, Selistre-de-Araujo, Heloisa S, Rhoades Sterling, Julie A
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 27-06-2021 MDPI
Subjects:	Animals Biomedical materials Bone cancer Bone growth Bone marrow bone metastasis Bone Neoplasms - genetics Bone Neoplasms - secondary Bone tumors Breast cancer Breast Neoplasms - genetics Breast Neoplasms - pathology Cell Line, Tumor Cell Movement Cell Proliferation Disease Models, Animal Extracellular matrix Female Flow cytometry Gene Expression Genotype & phenotype Humans Hypotheses Integrin alpha2beta1 - genetics integrin α2β1 Integrins Metastases Metastasis Mice Neoplasm Invasiveness Osteolysis Osteolysis - genetics Osteolysis - metabolism Pathogenesis Patients Phenotype Prostate cancer tumor-induced bone disease Tumors tumor-induced bone disease breast cancer integrin α2β1 bone metastasis
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Integrins participate in the pathogenesis and progression of tumors at many stages during the metastatic cascade. However, current evidence for the role of integrins in breast cancer progression is contradictory and seems to be dependent on tumor stage, differentiation status, and microenvironmental influences. While some studies suggest that loss of α2β1 enhances cancer metastasis, other studies suggest that this integrin is pro-tumorigenic. However, few studies have looked at α2β1 in the context of bone metastasis. In this study, we aimed to understand the role of α2β1 integrin in breast cancer metastasis to bone. To address this, we utilized in vivo models of breast cancer metastasis to bone using MDA-MB-231 cells transfected with an α2 expression plasmid (MDA-OEα2). MDA cells overexpressing the α2 integrin subunit had increased primary tumor growth and dissemination to bone but had no change in tumor establishment and bone destruction. Further in vitro analysis revealed that tumors in the bone have decreased α2β1 expression and increased osteolytic signaling compared to primary tumors. Taken together, these data suggest an inverse correlation between α2β1 expression and bone-metastatic potential. Inhibiting α2β1 expression may be beneficial to limit the expansion of primary tumors but could be harmful once tumors have established in bone.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms22136906