The glycosaminoglycan hyaluronic acid has been shown to be present at high concentrations in and around several highly invasive tumors. It has been postulated that this hyaluronic acid-rich extracellular matrix provides an embryonic-like environment conducive to cell migration. It has also long been postulated that stromal cells of the host tissue, immediately surrounding an invasive tumor, play a major role in the synthesis and deposition of this new matrix. The regulation of hyaluronic acid synthesis by tumor-host cell interactions during tumor invasion is the overall goal of this proposal. Human lung carcinoma cells in culture have been shown to contain a factor on their cell surface which interacts with normal cells, such as fibroblasts, to induce a stimulation of hyaluronic acid synthesis. The factor has been extracted from the membranes in an active form and partially purified. The temporal and spatial localization of this factor in tumor tissues, at various stages of invasion, will serve as a probe into the role of tumor-host cell interactions during invasion.
The aim of this proposal is therefore to continue to purify this factor, develop a monoclonal antibody against it, and use this antibody to immunohistologically stain sections of human tumor tissue of various types and invasive grade. This study forms part of the long term goal of the principal investigator to investigate tumor-induced alterations in the surrounding connective tissue stroma which promote tumor invasion and metastasis.
