ASCO 233 (so I'm a little late)
Expression of activated integrin avb3 in clinical breast cancer metastasis
Melanie Rolli, Alan Saven, Jan Pilch, Valentina Russack, Brunhilde Felding-Habermann, The Scripps Research Institute, La Jolla, CA; Scripps Clinic, La Jolla, CA.
Purpose of this study is to analyze a clinical relevance of the expression of adhesion receptor integrin avb3 in a functionally activated form in metastatic breast cancer. We found earlier that breast cancer cells can express avb3 in an activated or a non-activated functional form. This was shown with in vivo and in vitro selected functional variants of the MDA-MB 435 human breast cancer cell line. Importantly, only cell variants expressing activated avb3, but not those expressing the non-activated receptor, were highly metastatic in immune deficient mice. Here, we analyzed the expression and functional activation state of integrin avb3 in primary metastatic cells from breast cancer patients. Primary metastatic cells were isolated from pleural effusions or peripheral blood samples of stage IV breast cancer patients. Circulating metastatic cells were captured with immuno-magnetic beads carrying monoclonal antibody BerEP4 against a human epithelial antigen. The established cell lines PE02JA (pleural effusion), BCM1, BCM2 and BMS (peripheral blood) were characterized by morphological criteria and expression of epithelial and breast carcinoma antigens. Each cell line expressed integrin avb3 and utilized the receptor to bind soluble ligand, undergo platelet mediated tumor cell arrest during blood flow and enhance migration toward extra cellular matrix proteins. Compared to defined functional variants of the MDA-MB 435 cell model, these results indicate that integrin avb3 is expressed on primary metastatic breast cancer cells in an activated functional form. Thus, the expression of activated avb3 serves as a functional marker in metastatic breast cancer cells. Based on its specific adhesive and ligand binding functions, activated integrin avb3 likely promotes breast cancer metastasis by mediating tumor cell arrest within the vasculature and by supporting breast cancer cell migration from the primary tumor and during extravasation from lymphatic or blood vessels
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1963
Bone marrow micrometastases in patients with breast cancer have upregulation of ICAM - 1 and á V â 3 compared to their primary tumours
Noel J Aherne, Eoghan T Condon, Juang H Wang, Karen C Redmond, Seamus O'Reilly, Henry P Redmond, Cork University Hospital, Cork, Ireland.
Introduction: Bone marrow micrometastases in patients with breast cancer may be detected by flow cytometry (FC) with human epithelial antigen (HEA). However, there is little known about the integrin profile of these micrometastatic epithelial cells. Methods: Using FC, the primary tumours of five patients with breast cancer were digested into a single cell suspension and then dual immunostained with HEA and the PE-labelled monoclonal antibodies to the integrins beta-1, p-selectin, ICAM-1 and ávâ3. Pre-operative bilateral bone marrow aspirates from the iliac crests were treated by ficoll-paque separation and the leucocyte fraction was isolated.1 x 10 [sup]5[/sup] cells were dual immunostained with FITC-conjugated HEA and the PE-labelled antibodies to the integrins beta-1, p-selectin, ICAM-1 and ávâ3. Results: FITC-conjugated HEA was widely expressed in all primary breast tumours, mean 80 % (range 45 %- 90 %).the mean ICAM-1 and ávâ3 expression in the primary tumours was 8.4 % and 0.5 % respectively. There was no beta-1 integrin or p-selectin expression in any sample. The mean ICAM-1 and ávâ3 expression in HEA positive micrometastatic cells was 28 % and 5.1 % respectively. There was no expression of beta-1 integrin or p-selectin in HEA-positive cells in any bone marrow sample. Conclusion: this study provides a novel insight into the adhesion molecule profile of micrometastatic epithelial cells in women with breast cancer. The upregulation of ICAM-1 and ávâ3 integrins reveals the pro-angiogenic nature of micrometastatic cells.
INTEGRIN EXPRESSION OF PRIMARY TUMOURS AND MICROMETASTASES
ICAM - 1
ÁVÂ3
TUMOUR
8.4 %
0.5 %
MICROMETASTASES
28.0 %
5.0 % |
