RRC ID 45121
Author Tomioka Y, Morimatsu M, Nishijima K, Usui T, Yamamoto S, Suyama H, Ozaki K, Ito T, Ono E.
Title A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice.
Journal Biochem Biophys Res Commun
Abstract Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell growth and negative immunomodulation. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor molecules like human Siglec-9, leading to provide antitumor benefit against MUC1-expressing tumor, and generated transgenic mouse lines expressing sSiglec-9 (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower histological malignancy as compared with non-transgenic mice. The sSiglec-9 was detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9 and MUC1 were often colocalized on surfaces of the tumor cells. PCNA immunohistochemistry also revealed the reduced proliferation of the tumor cells in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor proliferation, MUC1 expressions were tend to be reduced. In the ascites of sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas aggregations of degenerative T cells were often observed in the non-transgenic mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1-expressing tumor in the transgenic mice, which may avoid the negative immunomodulation and/or suppress tumor-associated MUC1 downstream signal transduction, and subsequent tumor proliferation.
Volume 450(1)
Pages 532-7
Published 2014-7-18
DOI 10.1016/j.bbrc.2014.06.009
PII S0006-291X(14)01061-4
PMID 24924635
MeSH Animals Antigens, CD / chemistry Antigens, CD / genetics Antigens, CD / metabolism* Antigens, Differentiation, B-Lymphocyte / chemistry Antigens, Differentiation, B-Lymphocyte / genetics Antigens, Differentiation, B-Lymphocyte / metabolism* Cell Line, Tumor Cell Survival Female Humans Mammary Neoplasms, Animal / metabolism* Mammary Neoplasms, Animal / pathology Mammary Neoplasms, Animal / therapy* Mice Mice, Inbred C57BL Mice, Transgenic Mucin-1 / genetics Mucin-1 / metabolism* Solubility
IF 2.985
Times Cited 10
WOS Category BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells