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Attachment
Characteristics and Involvement of Integrins in Adhesion of Breast Cancer
Cell Lines to Extracellular Bone Matrix Components |
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Gabri van der
Pluijm, Hans Vloedgraven, Socrates Papapoulos, Clemens Löwik, Wojtek
Grzesik, Janet Kerr, and Pamela Gehron Robey |
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Department
of Endocrinology (GvdP, HV, SP, CL), University Hospital, Leiden, The Netherlands;
and National Institute of Dental Research, Craniofacial and Skeletal Disease
Branch (WG, PGR), National Institutes of Health, Bethesda, Maryland |
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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
[mu]g/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. |
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