A comparative analysis of oncofetal fibronectin and tenascin-C incorporation in tumour vessels using human recombinant SIP format antibodies

Abstract

Tumour angioneogenesis is associated with the reexpression of oncofetal fibronectin (oncFn) and tenascin-C (oncTn-C) splice variants, which may serve as targets for antibody-based pharmacodelivery. Knowledge of the vascular distribution and organization in different tumours is of importance for the understanding of tumour vessel formation and might be crucial for therapy. Therefore, human SIP format antibodies against Fn ED-A, Fn ED-B and Tn-C A and C splice domains were used for immunofluorescence labelling in renal, lung, oral, colon, breast and urinary bladder carcinoma specimens and in a renal carcinoma xenograft. The spatial relation to stroma, vessels and vascular basement membrane (vBM) was analysed including CD31 and laminin alpha4 chain antibodies. Renal cell carcinomas and atypical carcinoid of the lung revealed vessel-restricted oncFn and/or oncTn-C depositions; all other entities showed a variable stroma positivity including vessels. The individual pattern of oncFn/oncTn-C incorporation in the vBM depended on tumour type, vessel size and intratumoural heterogeneity. There was a stratification of the vessel wall showing luminal oncFn and extraluminal oncTn-C depositions. As shown in the xenograft, perivascular oncTn-C is provided by carcinoma cells. In conclusion, tumours differ in the pattern of Fn or Tn-C isoform positivity in the vessel wall, potentially representing a tumour type specific endothelial cell-tumour cell-stromal cell interaction. Carcinoma cells themselves are involved in vascular Tn-C matrix organization. Up to antigen distribution, Fn and Tn-C domain antibodies may serve as vehicles for antiangiogenetic and antifibrotic agents; oncFn/oncTn-C based targeting should be adapted individually.