In vivo Heparan Sulfate Treatment Alters the Immune Response of Normal and LLC-Bearing Mice

Abstract

Despite the large amount of research dedicated to the understanding and treatment of tumor growth, the majority of cancers continue to lack effective therapeutic options. As in the case of most solid tumors, growth requires evasion of the host immune system. Our previous work using the Lewis Lung Carcinoma (LLC) model of tumor bearing (TB)-mice has shown several tumor-induced immune suppressing effects to be present. These effects include a decreased T-cell proliferative response to Con A and altered cytokine secretion patterns that favor neither a Th1 nor a Th2 response. To address these immune alterations, immune modulating approaches have been a central area of study. Of the many potential immune modulating compounds, we believe promising therapeutic potential lies in the heparin family. Heparan sulfate (HS), in particular, has been shown to increase T-cell proliferative response in non TB-mouse splenocytes as well as promotion of a beneficial Th1 response. In this paper, we studied the potential of HS to decrease tumor burden via in vivo treatment of TB-mice. Results showed both normal and TB-mice splenocytes had a dose response change in proliferation as a result of HS treatment. Furthermore, splenocytes from HS treated TB-mice showed a potentially beneficial decrease in basal level proliferation. On gross examination, HS treatment produced a decrease in tumor surface necrosis with a visible (2 ± 1.8%) surface necrotic area in treated mice as opposed to a (43 ± 16%) surface necrotic area in untreated mice. HS treatment decreased TB-mice splenomegaly when comparing mice spleen weights in treated (0.3 ± 0.05 g) vs. untreated (0.14 ± 0.02 g) groups. These results show a potential role of HS as an immune modulating agent with antitumor properties.

Key Words :

• Heparan Sulfate
• Lewis Lung Carcinoma
• Tumor
• T-cells
• Lung Cancer