Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid correlates with lymphatic invasion and lymph node metastasis.

Background: Association studies have implicated the glycosaminoglycan hyaluronan (hyaluronic acid, HA) and its degrading enzymes the hyaluronidases in tumour progression and metastasis. Oligosaccharides of degraded HA have been ascribed a number of biological functions that are not exerted by high-molecular-weight HA (HMW-HA). However, whether these small HA oligosaccharides (sHA) have a role in tumour progression currently remains uncertain due to an inability to analyse their concentration in tumours.

Inhibition of VEGFR-3 activation in tumor-draining lymph nodes suppresses the outgrowth of lymph node metastases in the MT-450 syngeneic rat breast cancer model.

For many types of human cancer, the expression of vascular endothelial growth factor-C (VEGF-C) correlates with enhanced tumor-associated lymphatic vessel density, metastasis formation and poor prognosis. In experimental animals, VEGF-C produced by primary tumors can induce lymphangiogenesis within and/or at the periphery of the tumor, and promotes metastasis formation. Tumor-induced lymphangiogenesis is therefore thought to expedite entry of tumor cells into the lymphatic vasculature and their trafficking to regional lymph nodes, thereby fostering metastatic dissemination.

Lovastatin inhibits proliferation of pancreatic cancer cell lines with mutant as well as with wild-type K-ras oncogene but has different effects on protein phosphorylation and induction of apoptosis.

Besides its pharmacological effect on cholesterol biosynthesis, lovastatin inhibits p21ras proteins by substrate depletion for post-translational protein farnesylation and geranylation. This inhibition has previously been used to reverse cell proliferation after cellular transformation by the mutant p21ras oncogene. We investigated the biological effects of lovastatin on two pancreatic carcinoma cell lines.