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Title
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Claudin-2 promotes colorectal cancer liver metastasis and is a biomarker of the replacement type growth pattern
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Communications Biology
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Publication
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Nature Publishing Group
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2021
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ISSN
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2399-3642
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DOI
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10.1038/S42003-021-02189-9
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Volume/pages
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4
:1
(2021)
, 14 p.
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Article Reference
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657
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ISI
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000663720000006
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Pubmed ID
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34079064
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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