Attachment characteristics and involvement of integrins in adhesion of breast cancer cell lines to extracellular bone matrix components.
Evidence is mounting that changes in the ability of cancer cells to adhere to extracellular matrices play a decisive role in metastatic spread. The mechanism underlying the preference of breast cancer cells to metastasize to bone is, however, poorly understood. We investigated the expression and involvement of integrin adhesion receptors in the adhesion of breast cancer cells to bone matrix (constituents) in two in vitro attachment assays using RGD peptides and anti-integrin antibodies. Breast cancer cells adhered rapidly to extracellular bone matrix. Adhesion of most cells to vitronectin, fibronectin, thrombospondin, osteopontin, and the fairly bone-specific bone sialoprotein was inhibited by the 200 micrograms/ml GRGDS peptide. These data suggest that integrin adhesion receptors can modulate the attachment of breast cancer cells to bone matrix molecules. In accordance with these findings, we found that alpha 1-alpha 5(beta 1) and alpha v(beta 3) integrins were expressed by mammary carcinoma cells. Highly tumorigenic MDA-MB-231 cells, which form osteolytic metastases in vivo, expressed relatively high levels of alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 3 integrins, when compared to MCF-7, T47D, and ZR75-1 breast cancer cells. Addition of function-blocking anti-alpha 2 beta 1, -alpha 3 beta 1, -alpha 5 beta 1, and -alpha v beta 3 antibodies significantly inhibited the adhesion of MDA-MB-231 breast cancer cells to bone matrices. In conclusion, our data suggest a possible role for beta 1 and beta 3 integrin subfamily members in the establishment of skeletal metastases in advanced breast cancer patients. Clearly, functional evidence is required to understand the mechanisms involved in the development of skeletal metastases in breast cancer patients.
van der Pluijm
Department of Endocrinology, University Hospital, Leiden, The Netherlands.
Vloedgraven
H
H
Papapoulos
S
S
Löwick
C
C
Grzesik
W
W
Kerr
J
J
Robey
P G
PG
D001842:Bone and Bones / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016023:Integrins