Tumor growth and development is influenced by its microenvironment. A major extracellular matrix molecule involved in
cancer progression is
hyaluronan (HA).
Hyaluronan and expression of a number of hyaladherin family
proteins are dramatically increased in many
cancer malignancies. One such hyaladherin,
hyaluronan-binding protein 1 (HABP1/p32/gC1qR) has been considered to be a
biomarker for
tumor progression. Interestingly, overexpression of HABP1 in fibroblast has been shown to increase autophagy via generation of excess
reactive oxygen species (ROS) and depletion of HA leading to apoptosis. Cancerous cells are often found to exhibit decreased rate of proteolysis/autophagy in comparison to their normal counterparts. To determine if HABP1 levels alter tumorigenicity of cancerous cells, HepR21, the stable transfectant overexpressing HABP1 in HepG2 cell line was derived. HepR21 has been shown to have increased proliferation rate than HepG2, intracellular HA cable formation and enhanced
tumor potency without any significant alteration of intracellular ROS. In this paper we have observed that HepR21 cells containing higher endogenous HA levels, have downregulated expression of the autophagic marker, MAP-LC3, consistent with unaltered levels of endogenous ROS. In fact, HepR21 cells seem to have significant resistance to exogenous ROS stimuli and
glutathione depletion. HepR21 cells were also found to be more resilient to nutrient
starvation in comparison to its parent cell line. Decline in intracellular HA levels and HA cables in HepR21 cells upon treatment with HAS inhibitor (4-MU), induced a surge in ROS levels leading to increased expression of MAP-LC3 and
tumor suppressors
Beclin 1 and PTEN. This suggests the importance of HABP1 induced HA cable formation in enhancing
tumor potency by maintaining the
oxidant levels and subsequent autophagic vacuolation.