Effects of down-regulating the Id genes in human colorectal cancer cells on early steps of haematogenous metastasis.
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.
Okaji
Yurai
Y
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
Tsuno
Nelson Hirokazu
NH
Kitayama
Joji
J
Sakurai
Daisuke
D
Tsuchiya
Naoyuki
N
Saito
Shinsuke
S
Takegami
Kenji
K
Tsuchiya
Takeshi
T
Kawai
Kazushige
K
Yazawa
Kentaro
K
Asakage
Masahiro
M
Yoneyama
Satomi
S
Yamada
Jun
J
Tokunaga
Katsushi
K
Takahashi
Koki
K
Nagawa
Hirokazu
H
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
D015815:Cell Adhesion Molecules; D051796:Inhibitor of Differentiation Proteins; D007797:Laminin