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- Title
Claudin-2 promotes colorectal cancer liver metastasis and is a biomarker of the replacement type growth pattern.
- Authors
Tabariès, Sébastien; Annis, Matthew G.; Lazaris, Anthoula; Petrillo, Stephanie K.; Huxham, Jennifer; Abdellatif, Amri; Palmieri, Vincent; Chabot, Jaclyn; Johnson, Radia M.; Van Laere, Steven; Verhoef, Cornelis; Hachem, Yasmina; Yumeen, Sara; Meti, Nicholas; Omeroglu, Atilla; Altinel, Gulbeyaz; Gao, Zu-Hua; Yu, Alan S. L.; Grünhagen, Dirk J.; Vermeulen, Peter
- Abstract
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. Tabariès 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.
- Subjects
COLORECTAL cancer; CLAUDINS; BIOMARKERS; XENOGRAFTS; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-02189-9