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CCR4 mediates CCL17 (TARC)-induced migration of human colon cancer cells via RhoA/Rho-kinase signaling.

Al-Haidari, Amr LU ; Syk, Ingvar LU ; Jirström, Karin LU and Thorlacius, Henrik LU (2013) In International Journal of Colorectal Disease 28(11). p.1479-1487
Abstract
BACKGROUND: Accumulating data suggest a role of chemokines in tumor cell metastasis. CCR4 has been implicated in hematologic malignancies and recently also in solid tumors. Herein, we hypothesized that CCR4 might be expressed and support migration of colon cancer cells. METHODS: We used quantitative RT-PCR and flow cytometry to determine mRNA and surface expression of CCR4 on colon cancer cell lines (HT-29) and (AZ-97). Total RhoA and active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using ELISA and G-LISA assays. Migration assays were performed to evaluate colon cancer cells chemotaxis. In vitro tumor growth was assessed using proliferation assay. RESULTS: Our results show clear-cut mRNA levels and surface... (More)
BACKGROUND: Accumulating data suggest a role of chemokines in tumor cell metastasis. CCR4 has been implicated in hematologic malignancies and recently also in solid tumors. Herein, we hypothesized that CCR4 might be expressed and support migration of colon cancer cells. METHODS: We used quantitative RT-PCR and flow cytometry to determine mRNA and surface expression of CCR4 on colon cancer cell lines (HT-29) and (AZ-97). Total RhoA and active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using ELISA and G-LISA assays. Migration assays were performed to evaluate colon cancer cells chemotaxis. In vitro tumor growth was assessed using proliferation assay. RESULTS: Our results show clear-cut mRNA levels and surface expression of CCR4 on a colon cancer cell line (HT-29) and on tumor cells (AZ-97). CCR4 ligand CCL17 (TARC) was a potent stimulator of colon cancer cell migration. This CCL17-induced colon cancer cell migration was inhibited by pre-incubation of the colon cancer cells with an antibody directed against CCR4 or an antagonist against CCR4. CCL17-induced signaling in colon cancer cells revealed that CCL17 increased mRNA formation of RhoA-C in colon cancer cells. Our results also found that CCL17 increased total RhoA and active RhoA protein levels in colon cancer cells. The Rho-kinase inhibitor Y-27632 abolished CCL17-induced colon cancer cell chemotaxis. In addition, inhibition of isoprenylation by GGTI-2133 markedly reduced colon cancer cell migration triggered by CCL17. CONCLUSIONS: Our novel data indicate for the first time that the CCL17-CCR4 axis might be involved in the spread of colon cancer cells. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
International Journal of Colorectal Disease
volume
28
issue
11
pages
1479 - 1487
publisher
Springer
external identifiers
  • wos:000325819200003
  • pmid:23649168
  • scopus:84891830636
  • pmid:23649168
ISSN
1432-1262
DOI
10.1007/s00384-013-1712-y
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000), Surgery Research Unit (013242220)
id
ab328f82-71b1-4523-9d2c-d2ca7cb4030e (old id 3804839)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23649168?dopt=Abstract
date added to LUP
2016-04-01 10:58:10
date last changed
2020-01-12 06:28:04
@article{ab328f82-71b1-4523-9d2c-d2ca7cb4030e,
  abstract     = {BACKGROUND: Accumulating data suggest a role of chemokines in tumor cell metastasis. CCR4 has been implicated in hematologic malignancies and recently also in solid tumors. Herein, we hypothesized that CCR4 might be expressed and support migration of colon cancer cells. METHODS: We used quantitative RT-PCR and flow cytometry to determine mRNA and surface expression of CCR4 on colon cancer cell lines (HT-29) and (AZ-97). Total RhoA and active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using ELISA and G-LISA assays. Migration assays were performed to evaluate colon cancer cells chemotaxis. In vitro tumor growth was assessed using proliferation assay. RESULTS: Our results show clear-cut mRNA levels and surface expression of CCR4 on a colon cancer cell line (HT-29) and on tumor cells (AZ-97). CCR4 ligand CCL17 (TARC) was a potent stimulator of colon cancer cell migration. This CCL17-induced colon cancer cell migration was inhibited by pre-incubation of the colon cancer cells with an antibody directed against CCR4 or an antagonist against CCR4. CCL17-induced signaling in colon cancer cells revealed that CCL17 increased mRNA formation of RhoA-C in colon cancer cells. Our results also found that CCL17 increased total RhoA and active RhoA protein levels in colon cancer cells. The Rho-kinase inhibitor Y-27632 abolished CCL17-induced colon cancer cell chemotaxis. In addition, inhibition of isoprenylation by GGTI-2133 markedly reduced colon cancer cell migration triggered by CCL17. CONCLUSIONS: Our novel data indicate for the first time that the CCL17-CCR4 axis might be involved in the spread of colon cancer cells.},
  author       = {Al-Haidari, Amr and Syk, Ingvar and Jirström, Karin and Thorlacius, Henrik},
  issn         = {1432-1262},
  language     = {eng},
  number       = {11},
  pages        = {1479--1487},
  publisher    = {Springer},
  series       = {International Journal of Colorectal Disease},
  title        = {CCR4 mediates CCL17 (TARC)-induced migration of human colon cancer cells via RhoA/Rho-kinase signaling.},
  url          = {https://lup.lub.lu.se/search/ws/files/2275401/4092400.pdf},
  doi          = {10.1007/s00384-013-1712-y},
  volume       = {28},
  year         = {2013},
}