Abstract | BACKGROUND & AIMS: METHODS & RESULTS: Quantitative immunofluorescence histochemistry showed that the expression level of the actinin-4 protein was increased in 73.1% (19/26) of the cases of colorectal cancer over the corresponding normal intestinal epithelium. The increased expression of actinin-4 was most significant in dedifferentiated cancer cells at the invasive front. A colorectal cancer cell clone capable of inducing actinin-4 using the tetracycline-regulatory system (designated DLD1 Tet-off ACTN-4) was established. Upon the induction of actinin-4, DLD1 Tet-off ACTN-4 cells spread filopodia and significantly increased their motility ( P = .00027); actinin-4 protein was concentrated at the leading edges of these actin-rich podia. When injected into the mesocecum of severe combined immunodeficient mice, DLD1 Tet-off ACTN4 cells, but not the control cells, metastasized into regional mesenteric lymph nodes, resembling the behavior of clinical cancers. The expression of actinin-4 in focally dedifferentiated cancer cells at the invasive front was significantly correlated with the frequency of lymph node metastasis of colorectal cancer ( P = .038). CONCLUSIONS:
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Authors | Kazufumi Honda, Tesshi Yamada, Yasuharu Hayashida, Masashi Idogawa, Satoshi Sato, Fumio Hasegawa, Yoshinori Ino, Masaya Ono, Setsuo Hirohashi |
Journal | Gastroenterology
(Gastroenterology)
Vol. 128
Issue 1
Pg. 51-62
(Jan 2005)
ISSN: 0016-5085 [Print] United States |
PMID | 15633123
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ACTN4 protein, human
- Biomarkers, Tumor
- Microfilament Proteins
- Actinin
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Topics |
- Actinin
(biosynthesis)
- Animals
- Biomarkers, Tumor
(biosynthesis)
- Cell Line, Tumor
- Cell Movement
(physiology)
- Colorectal Neoplasms
(metabolism, pathology, physiopathology)
- Cytoskeleton
(metabolism)
- Humans
- Lymphatic Metastasis
- Mice
- Mice, SCID
- Microfilament Proteins
(biosynthesis)
- Neoplasm Invasiveness
- Neoplasm Metastasis
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