Desmoplastic tumour-associated stroma versus neural tissue in central nervous system metastasis: effects of different microenvironments on tumour growth.

ABSTRACT

AIMS: Interactions between tumour cells and extracellular matrix (ECM) are critical in the metastatic cascade. We compared effects of desmoplastic stroma versus neural tissue on central nervous system (CNS) metastasis. METHODS AND RESULTS: Using integrins (ECM receptors), ECM (fibronectin, laminin and collagen IV) and CD31 and vascular endothelial growth factor (VEGF) for angiogenesis, this study examined immunohistochemically 69 consecutive cases of CNS metastases. In contrast to low-level expression in tumour-embedded neural tissue, ECM [fibronectin (71%), laminin γ-1 (79%) and collagen IV (92%)] and CD31-positive microvascular densities (33 versus 4 vessels/field) were significantly richer in desmoplastic tumour stroma, which was present in 90% (53 of 59) of carcinomas, 100% (five of five) of malignant melanomas and 100% (two of two) of sarcomas. Collagen IV expression in tumour stroma was correlated with the expression of fibronectin (P = 0.013) and laminin (P = 0.034) and with infiltrative tumour edges (P = 0.005); fibronectin-positive tumour stroma was correlated with a higher microvascular density (P = 0.015). In addition, tumour cells expressed integrins (∼75%) and laminin (84%) more frequently than VEGF (23%), and tumour expression of laminin was correlated with the presence of desmoplastic stroma (P = 0.006). Interestingly, laminin-positive tumour stroma was a worse prognosticator (P = 0.072). CONCLUSIONS: ECM- and vascular-rich stroma is important in tumour growth, which underlies therapeutic strategies targeting tumour-associated stroma.