The
proteoglycan versican is implicated in growth and
metastases of several
cancers. Here we investigated a potential contribution of stromal
versican to
tumor growth and angiogenesis. We initially determined
versican expression by several
cancer cell lines. Among these, MDA-MB231 and B16F10 had none to minimal expression in contrast to
Lewis lung carcinoma (LLC). Notably,
tumors arising from these cell lines had higher
versican levels than the cell lines themselves suggesting a contribution from the host-derived
tumor stroma. In LLC-derived
tumors, both the
tumor and stroma expressed
versican at high levels. Thus,
tumor stroma can make a significant contribution to
tumor versican content.
Versican localized preferentially to the vicinity of
tumor vasculature and macrophages in the
tumor. However, an
ADAMTS protease-generated
versican fragment uniquely localized to vascular endothelium. To specifically determine the impact of host/stroma-derived
versican we therefore compared growth of
tumors from B16F10 cells, which produced littleversican, in Vcan hdf/+ mice and wild-type littermates.
Tumors in Vcan hdf/+ mice had reduced growth with a lower capillary density and accumulation of capillaries at the
tumor periphery. These findings illustrate the variability of tumor cell line expression of
versican, and demonstrate that
versican is consistently contributed by the stromal tissue, where it contributes to
tumor angiogenesis.