title: A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice.
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.
authors.affiliation: Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan; Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. Electronic address: ytomi@muses.tottori-u.ac.jp.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tomioka
authors.affiliation: Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan; Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Electronic address: mmorimat@vetmed.hokudai.ac.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Morimatsu
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan. Electronic address: nishijma@nubio.nagoya-u.ac.jp.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nishijima
authors.affiliation: Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. Electronic address: usutatsu@muses.tottori-u.ac.jp.
authors.forename: Tatsufumi
authors.initials: T
authors.lastname: Usui
authors.affiliation: Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: ysayo@anim.med.kyushu-u.ac.jp.
authors.forename: Sayo
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: sharuka@anim.med.kyushu-u.ac.jp.
authors.forename: Haruka
authors.initials: H
authors.lastname: Suyama
authors.affiliation: Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: k-ozaki@anim.med.kyushu-u.ac.jp.
authors.forename: Kinuyo
authors.initials: K
authors.lastname: Ozaki
authors.affiliation: Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. Electronic address: toshiito@muses.tottori-u.ac.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ito
authors.affiliation: Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan; Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Biomedicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: etsuro@anim.med.kyushu-u.ac.jp.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ono
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D012995:Solubility
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D018396:Mucin-1; C422908:Siglece protein, mouse; C577056:muc1 protein, mouse
keywords: Antitumor benefit; MUC1; Mammary tumor; Soluble Siglec-9; Transgenic mice