94P CD44v6: A potential therapeutic target for liver carcinoma

نویسندگان

چکیده

Liver cancer has a poor prognosis predominantly resulting from tumour heterogeneity and limited treatment options. The two predominant types of liver are Hepatocellular carcinoma (HCC) Intrahepatic Cholangiocarcinoma (iCCA). CD44v6, splice variant the hyaluronic acid receptor CD44, is marker for stem cells, known to impact formation metastasis in several cancers. expression CD44v6 dramatically increases epithelial cells upon carcinogen exposure. With this study, we aim target primary human cell lines by using small peptide inhibitor, observe effects inhibition on migration, invasion EMT. was investigated mouse tissue immunohistochemistry. In addition, used HCC CC study role We observed CD44v6+ premalignant livers transgenic models with chronic damage. patterns differed models, where had hepatocyte-like phenotype some cholangiocyte-like others. Deletion Trp53 resulted significant increase number cells. also increased murine tumours compared liver, coincided Sox9 tumours. Human were analysed CD44 found have high (85-90%). Functional assays (clonogenic assay, wound healing assay transwell migration assay) performed lines. Treatment AMC303 conferred reduction potential Inhibition colony indicating decrease stemness characteristics A EMT both 2D 3D culture observed. led chemotaxis, summary, appears be promising targetable candidate carcinoma.

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ژورنال

عنوان ژورنال: Annals of Oncology

سال: 2022

ISSN: ['0923-7534', '1569-8041']

DOI: https://doi.org/10.1016/j.annonc.2022.09.095