Hyaluronic acid stimulates tumor-cell proliferation at wound sites

For EMR, the submucosal injection of sodium hyaluronate has become popular, because this substance creates a more prominent and longer-lasting mucosal protrusion than normal saline solution. However, the effects of sodium hyaluronate on tumor growth at wound sites remain unclear.For these experiments, a murine model with artificial wounds was used. Forty mice were randomly divided into two groups according to the substance to be injected into a wound: a sodium hyaluronate group and a control group. Tumors were created by inoculation of transplantable adenocarcinoma cell line colon 26. Two weeks later, the size, weight, proliferating cell nuclear antigen-labeling index, and CD44 expression of the subcutaneous tumors were compared between the two groups of mice.There were significantly greater increases in the growth and the weight of subcutaneous tumors in the sodium hyaluronate group compared with the control group. The PCNA-labeling index of cancer cells also was higher in the sodium hyaluronate group. Immunohistochemistry and Western blot analysis demonstrated that the CD44 protein expression of cancer cells was higher in the sodium hyaluronate group vs. the control group.In this study, sodium hyaluronate enhanced both tumor growth and CD44 expression of cancer cells at wound sites, suggesting that the use of sodium hyaluronate for EMR might stimulate the growth of residual tumor cells.