title: Effects of down-regulating the Id genes in human colorectal cancer cells on early steps of haematogenous metastasis.
abstract: Id genes (inhibitor of DNA binding/differentiation) play important roles in tumour growth. We have previously described crucial roles of Id gene over-expression in endothelial cells for tumour angiogenesis. Here, we have evaluated direct effects of Id gene down-regulation on tumour cells, namely on cell proliferation, motility, and adhesion to lung microvasculature during haematogenous metastasis. For this purpose, Id genes were stably down-regulated by RNA interference in human colorectal cancer cells. These cells showed delayed proliferation, inhibited motility and decreased expression of integrin alpha6 and consequently reduced adhesion to lung microvasculature in mice. Static adhesion assays and laminar flow assays revealed decreased laminin binding capacity of these cells, and blocking experiments confirmed that it could be attributed to decreased expression of integrin alpha6. The present results indicate important roles of Id genes in tumour cells during early steps of haematogenous metastasis and suggest dual effects from their therapeutic inhibition.
authors.affiliation: Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. okaji-tky@umin.ac.jp
authors.forename: Yurai
authors.initials: Y
authors.lastname: Okaji
authors.forename: Nelson Hirokazu
authors.initials: NH
authors.lastname: Tsuno
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakurai
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Takegami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kawai
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yazawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asakage
authors.forename: Satomi
authors.initials: S
authors.lastname: Yoneyama
authors.forename: Jun
authors.initials: J
authors.lastname: Yamada
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Koki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D019337:Hematologic Neoplasms / Q000209:etiology*; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
chemical_list: D015815:Cell Adhesion Molecules; D051796:Inhibitor of Differentiation Proteins; D007797:Laminin