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Adhesion of aspirated tumor cells to extracellular matrix proteins: a new methodology utilizing fine-needle
1Department of Pathology, University of Texas Southwestern Medical School, Dallas, USA.
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 article describes a new approach to the evaluation of tumor cell-matrix interactions by utilizing fine-needle aspiration of resected tumors.
Methods:
Fine-needle aspiration was performed on 15 fresh surgical specimens of various types of carcinomas. After partial purification by isotonic Percoll centrifugation, tumor cell adhesion to collagen Type IV, laminin, and fibronectin was evaluated by counting cytologically malignant cells adhering to matrix-coated plastic substrates. Frozen tissue sections of the corresponding tumors were studied simultaneously for immunohistochemical expression of alpha-2, alpha-3, alpha-4, and alpha-5 integrin subunit expression. Results of the immunohistochemical staining then were compared with the adhesion data for particular tumors.
Results:
In general, the majority of the tumors exhibited little or no adhesion to collagen or laminin, but several tumors showed marked adhesion to fibronectin. Striking differences were noted between some tumors of the same histologic subtype. Competitive inhibition studies performed with two of the tumors (a large cell carcinoma and a renal cell carcinoma) showed decreased 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 mediating the adhesion of these tumors to fibronectin. All the tumors examined exhibited strong immunohistochemical expression of the alpha-2 and alpha-3 integrin subunits, and all were negative for alpha-4. Three of the tumors showed 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 suspensions prepared from fine-needle aspirates, and there are marked differences in adhesive properties between particular tumors. Although two of the tumors showed a correlation between adhesion to fibronectin and immunohistochemical expression of the alpha-5 integrin subunit, matrix adhesion does not necessarily correlate with immunohistochemical expression of adhesion molecule receptors. In the future, this methodology potentially could be of value in determining which patients may benefit from therapies aimed at modifying tumor cell-matrix interactions.