Claudin-2 promotes colorectal cancer liver metastasis and is a biomarker of the replacement type growth pattern

被引：40

作者：

Tabaries, Sebastien ^{[1
,2
]}

Annis, Matthew G. ^{[1
,2
]}

Lazaris, Anthoula ^{[3
]}

Petrillo, Stephanie K. ^{[3
]}

Huxham, Jennifer ^{[1
,2
]}

Abdellatif, Amri ^{[3
]}

Palmieri, Vincent ^{[3
]}

Chabot, Jaclyn ^{[3
]}

Johnson, Radia M. ^{[4
]}

Van Laere, Steven ^{[5
,6
]}

Verhoef, Cornelis ^{[7
]}

Hachem, Yasmina ^{[1
]}

Yumeen, Sara ^{[1
]}

Meti, Nicholas ^{[1
]}

Omeroglu, Atilla ^{[8
]}

Altinel, Gulbeyaz ^{[8
]}

Gao, Zu-Hua ^{[8
]}

Yu, Alan S. L. ^{[9
]}

Grunhagen, Dirk J. ^{[7
]}

Vermeulen, Peter ^{[5
,6
]}

Metrakos, Peter ^{[3
]}

Siegel, Peter M. ^{[1
,2
]}

机构：

[1] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ, Canada

[2] McGill Univ, Dept Med, Montreal, PQ, Canada

[3] McGill Univ, Dept Surg, Hlth Ctr, Montreal, PQ, Canada

[4] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA

[5] Univ Antwerp, Mol Imaging Pathol Radiotherapy & Oncol MIPRO, Antwerp, Belgium

[6] Oncol Ctr GZA, Translat Canc Res Unit, Antwerp, Belgium

[7] Erasmus MC Canc Inst, Dept Surg Oncol, Rotterdam, Netherlands

[8] McGill Univ, Dept Pathol, Hlth Ctr, Montreal, PQ, Canada

[9] Univ Kansas, Med Ctr, Jared Grantham Kidney Inst, Kansas City, KS 66103 USA

来源：

COMMUNICATIONS BIOLOGY | 2021年 / 4卷 / 01期

基金：

加拿大健康研究院;

关键词：

BREAST-CANCER; EXTRACELLULAR VESICLES; GASTRIC-CANCER; EXPRESSION; CELLS; RESISTANCE; EXOSOMES; TUMORIGENICITY; INFLAMMATION; INVASION;

D O I：

10.1038/s42003-021-02189-9

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cancer cell survival. We now demonstrate that Claudin-2 is functionally required for colorectal cancer liver metastasis and that Claudin-2 expression in primary colorectal cancers is associated with poor overall and liver metastasis-free survival. We have examined the role of Claudin-2, and other claudin family members, as potential prognostic biomarkers of the desmoplastic and replacement histopathological growth pattern associated with colorectal cancer liver metastases. Immunohistochemical analysis revealed higher Claudin-2 levels in replacement type metastases when compared to those with desmoplastic features. In contrast, Claudin-8 was highly expressed in desmoplastic colorectal cancer liver metastases. Similar observations were made following immunohistochemical staining of patient-derived xenografts (PDXs) that we have established, which faithfully retain the histopathology of desmoplastic or replacement type colorectal cancer liver metastases. We provide evidence that Claudin-2 status in patient-derived extracellular vesicles may serve as a relevant prognostic biomarker to predict whether colorectal cancer patients have developed replacement type liver metastases. Such a biomarker will be a valuable tool in designing optimal treatment strategies to better manage patients with colorectal cancer liver metastases. Tabaries et al. describe that claudin 2 is a promoter of colorectal cancer liver metastasis. Furthermore, high Claudin-2 expression is associated with shorter time to liver-specific recurrence and is a biomarker of replacement type CRC liver metastases.

引用

页数：14

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