Adhesion of aspirated tumor cells to extracellular matrix proteins - A newmethodology utilizing fine-needle aspiration

BACKGROUND. Cell adhesion molecules mediate the interactions of cells with other cells and with extracellular matrix components. Such interactions may be important in the development of tumor invasion and metastasis. This art icle describes a new approach to the evaluation of tumor cell-matrix intera ctions by utilizing fine-needle aspiration of resected tumors. METHODS. Fine-needle aspiration was performed on 15 fresh surgical specimen s of various types of carcinomas. After partial purification by isotonic Pe rcoll centrifugation, tumor cell adhesion to collagen Type nr, laminin, and fibronectin was evaluated by counting cytologically malignant cells adheri ng to matrix-coated plastic substrates. Frozen tissue sections of the corre sponding tumors were studied simultaneously for immunohistochemical express ion of alpha-2, alpha-3, alpha-4, and alpha-5 integrin subunit expression. Results of the immunohistochemical staining then were compared with the adh esion data for particular tumors. RESULTS. In general, the majority of the turners exhibited little or no adh esion to collagen or laminin, but several tumors showed marked adhesion to fibronectin. Striking differences were noted between some tumors of the sam e histologic subtype. Competitive inhibition studies performed with two of the tumors (a large cell carcinoma and a renal cell carcinoma) showed decre ased adhesion to fibronectin in the presence of anti-alpha-5, suggesting at least a partial role for the alpha-5-beta 1 fibronectin receptor in mediat ing the adhesion of these tumors to fibronectin. All the tumors examined ex hibited strong immunohistochemical expression of the alpha-2 and alpha-3 in tegrin subunits, and all were negative for alpha-4. Three of the tumors sho wed weak expression of alpha-5, two of which (a squamous cell carcinoma and a renal cell carcinoma) were the tumors that showed the greatest adhesion to fibronectin. CONCLUSIONS. Quantitative adhesion data can be obtained using cell suspensi ons prepared from fine-needle aspirates, and there are marked differences i n adhesive properties between particular tumors. Although two of the tumors showed a correlation between adhesion to fibronectin and immunohistochemic al expression of the alpha-5 integrin subunit, matrix adhesion does not nec essarily correlate with immunohistochemical expression of adhesion molecule receptors. In the future, this methodology potentially could be of value i n determining which patients may benefit from therapies aimed at modifying tumor cell-matrix interactions. (C) 2000 American Cancer Society.