Antitumor efficacy of CC motif chemokine ligand 19 in colorectal cancer.
OBJECTIVE
To investigate the function of CC motif chemokine ligand 19 (CCL19) in colorectal cancer (CRC).


METHODS
Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry were performed separately to detect the expression of CCL19 in colorectal carcinoma tissues. The expression of CCL19 and its receptor (CCR7) in CRC cell lines were screened by Western blot. SW620, SW1116 and LoVo cell lines were screened and processed with recombinant human CCL19 (rhCCL19) or si-CCL19 RNA. Cell proliferation assay and transwell assay were performed to evaluate the proliferation, migration and invasion of CRC cells, respectively. And the role of proangiogenesis was checked by endothelial tube formation assay.


RESULTS
qRT-PCR, Western blot and immunohistochemistry revealed that both CCL19 mRNA and protein were obviously expressed in a lower degree in CRC tissues than normal tissues (P < 0.01). The CCL19 expression correlated with tumor size (P = 0.03) and invasion depth (P = 0.04) in a negative manner and CCL19-positive patients had longer lifespans (P < 0.05). SW620 and SW1116 cells were screened as CCL19/CCR7 high-expression cells, while LoVo was selected as CCL19/CCR7 low-expression cell among seven CRC cell lines by Western blot. The proliferation, migration, invasion and proangiogenesis of SW620 and SW1116 cells were distinctly suppressed after they were stimulated by rhCCL19 (P < 0.05), and the data presented dose-dependency. Oppositely, these abilities were significantly enhanced after CCL19 gene was silenced (P < 0.05). However, the effects of rhCCL19 and si-CCL19 RNA on LoVo were not significant (P > 0.05).


CONCLUSIONS
Our research findings indicate that CCL19 may play a suppressive role in colorectal tumorigenesis.
Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Second Ruijin Road, Shanghai, China.
Jun
J
Lu
Jingkun
J
Zhao
Hao
H
Feng
Puxiongzhi
P
Wang
Zhuo
Z
Zhang
Yaping
Y
Zong
Junjun
J
Ma
Minhua
M
Zheng
Aiguo
A
Lu
D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054415:Chemokine CCL19 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering; D054400:Receptors, CCR7 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D047368:Tumor Burden / Q000235:genetics
C515460:CCL19 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054400:Receptors, CCR7; D011994:Recombinant Proteins