| 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 |
|
