Aberrant expression of connexin 26 is associated with lung metastasis of colorectal cancer.

Abstract

PURPOSE:

Connexin 26 (Cx26) is one of the gap junction-forming family members classically considered to be tumor suppressors. However, recent studies show association of elevated expression of Cx26 with poor prognosis in several human malignancies. Furthermore, Cx26 has been observed to be indispensable to spontaneous metastasis of melanoma cells. Here, we assessed Cx26 expression in primary colorectal cancer (CRC) and the metastatic lesions to elucidate its role in metastasis.

EXPERIMENTAL DESIGN:

Cx26 expression was assessed in 25 adenomas, 167 CRCs, and normal mucosa, together with the metastatic lesions.

RESULTS:

Normal mucosa and adenomatous tissue expressed Cx26 mainly in the plasma membrane, whereas cancer cells mostly contained Cx26 in the cytoplasm. The incidence of aberrant Cx26 expression varied widely in CRC (mean, 49.5 +/- 35.5%), and the expression levels were confirmed by Western blot and quantitative reverse transcription-PCR. Clinicopathologic survey revealed association of high expression with less differentiated histology and venous invasion (P = 0.0053 and P = 0.0084, respectively). Notably, high Cx26 expression was associated with shorter disease-free survival and shorter lung metastasis-free survival in 154 curatively resected CRC sets (P = 0.041 and P = 0.028, respectively). Survey of metastatic lesions revealed that lung metastasis, but not liver and lymph nodes metastases, expressed higher Cx26 than the CRC series or corresponding primary CRCs (P < 0.0001 and P = 0.0001, respectively).

CONCLUSIONS:

These findings suggest that aberrant expression of Cx26 plays an essential role in lung metastasis. Thus, Cx26 is a promising therapeutic target, particularly for CRC patients who develop lung metastasis.

• Authors: Koji Ezumi, Hirofumi Yamamoto, Kohei Murata, Masahiko Higashiyama, Bazarragchaa Damdinsuren, Yurika Nakamura, Naganori Kyo, Jiro Okami, Chew Yee Ngan, Ichiro Takemasa, Masataka Ikeda, Mitsugu Sekimoto, Nariaki Matsuura, Hiroshi Nojima, Morito Monden
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 3 Pg. 677-84 (Feb 01 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18245526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Connexins
• DNA Primers
• GJB2 protein, human
• Connexin 26

Topics

• Adult
• Aged
• Aged, 80 and over
• Colorectal Neoplasms (genetics, pathology, surgery)
• Connexin 26
• Connexins (genetics)
• DNA Primers
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Intestinal Mucosa (pathology)
• Lung Neoplasms (genetics, pathology, secondary, surgery)
• Male
• Middle Aged
• Neoplasm Metastasis
• Polymerase Chain Reaction