THE POTENTIAL ROLE OF INTEGRIN RECEPTOR SUBUNITS IN THE FORMATION OF LOCAL RECURRENCE AND DISTANT METASTASIS BY MOUSE BREAST-CANCER CELLS

Background: The mechanisms by which surgical injury fosters tumor grow th are examined. Methods: TA3Ha mouse breast tumor line and its sublin e (TA3AD) differing in their metastatic abilities as tested by two mod els were used. In model a, TA3Ha/TA3AD tumors were grown in the mammar y fat pads of mice and then surgically removed with a curative intent. In model b, TA3Ha/TA3AD cells were injected intravenously into mice s ubjected to liver or spleen wedge resection. Frequency of tumor format ion at various sites was assessed. Expression of integrin, immunoglobu lin, and proteoglycan cell adhesion receptors on TA3Ha and TA3AD cells was examined by flow cytometry, The roles of these receptors in metas tasis were examined by blocking them by selected ligands and/or antibo dies. Results: Frequencies of local recurrence and axillary metastasis after surgical resection, were 43% (32/74), and 37% (27/74) with TA3H a rumors and 4% (1/29) at both sites with TA3AD tumors. Tumors at surg ically injured spleen and the liver were seen in 75% (141/189) and 45% (107/ 240) of the mice with TA3Ha cells and in 8% (3/38) and 10% (4/4 2) of the mice with TA3AD cells. alpha(5) and CD44 receptors were expr essed by TA3Ha cells but not by TA3AD cells. Other receptors examined were similarly expressed by both cell lines. Blocking of or, receptor by fibronectin reduced tumor implantation in a dose-dependent manner. Conclusions: The data suggest a correlation among the ability to impla nt at surgically injured sites, to form local recurrence, and to expre ss the fibronectin receptor subunit. (C) 1996 Wiley-Liss, Inc.