Membranous CD44v6 is upregulated as an early event in colorectal cancer: Downregulation is associated with circulating tumor cells and poor prognosis

Kataki, Agapi; Giannakoulis, Vassilis G.; Derventzi, Anastasia; Papiris, Konstantinos; Koniaris, Efthymios; Konstadoulakis, Manousos M.

doi:10.3892/ol.2021.13081

Cited by 6 publications

(1 citation statement)

References 36 publications

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“…Systematic assessment of the prognostic impact of mCD44v6 protein revealed that the loss of mCD44v6 is associated with lymph node metastasis and adverse prognosis with the reduction in mCD44v6 expression from the center of the tumor to its invasive front [7,29]. Downregulation of mCD44v6 is associated with the presence of circulating tumor cells (CTCs) [30].…”

Section: Discussionmentioning

confidence: 99%

CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas

Yoshida,

Kadota,

Yamada

et al. 2023

Clin Exp Med

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Background: CD44 and CD44 variant isoforms have been reported as contributing factors to cancer progression. In this study, we aimed to assess whether CD44 and its variant isoforms were correlated with the prognostic factors for distant metastasis in stage I lung adenocarcinomas using tissue microarray and immunohistochemistry.Methods: In this single-center retrospective study, we analyzed the data of 490 patients with stage I lung adenocarcinoma resected between 1999 and 2016. We constructed tissue microarrays and performed immunohistochemistry for CD44s, CD44v6, and CD44v9. The risk of disease recurrence and its associations with clinicopathological risk factors were assessed.Results: CD44v6 expression was signi cantly associated with recurrence. Patients with CD44v6-negative tumors had a signi cantly increased risk of developing distant recurrence than patients with CD44v6positive tumors (5-year cumulative incidence of recurrence (CIR), 10.7% vs. 4.6%; P = 0.009). However, CD44v6-negative tumors were not associated with an increased risk of locoregional recurrence compared to CD44v6-positive tumors (5-year CIR, 6.0% vs. 4.0%; P = 0.39). The overall survival (OS) of patients with CD44v6-negative tumors was signi cantly lower than that of patients with CD44v6-positive tumors (5year OS: 87% vs. 94%, P = 0.016). CD44v6-negative tumors were also associated with invasive tumor size and lymphovascular invasion.Conclusion: Even in stage I disease, tumors with negative-CD44v6 expression had more distant recurrences than those with positive-CD44v6 expression and were associated with poor prognosis in resected stage I lung adenocarcinomas. Thus, CD44v6 downregulation may be a prognostic factor for distant metastasis in stage I lung adenocarcinomas.

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Section: Discussionmentioning

confidence: 99%

CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas

Yoshida,

Kadota,

Yamada

et al. 2023

Clin Exp Med

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CD44v6 expression in gastroenteropancreatic neuroendocrine neoplasms: Clinicopathological correlation and prognosis

Nibhondhratana¹,

Watcharadetwittaya²,

Sa-Ngiamwibool³

2022

Pathology - Research and Practice

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Selection, characterization and in vivo evaluation of novel CD44v6-targeting antibodies for targeted molecular radiotherapy

Mortensen,

Berglund,

Segerström

et al. 2023

Sci Rep

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Molecular radiotherapy combines the advantages of systemic administration of highly specific antibodies or peptides and the localized potency of ionizing radiation. A potential target for molecular radiotherapy is the cell surface antigen CD44v6, which is overexpressed in numerous cancers, with limited expression in normal tissues. The aim of the present study was to generate and characterize a panel of human anti-CD44v6 antibodies and identify a suitable candidate for future use in molecular radiotherapy of CD44v6-expressing cancers. Binders were first isolated from large synthetic phage display libraries containing human scFv and Fab antibody fragments. The antibodies were extensively analyzed through in vitro investigations of binding kinetics, affinity, off-target binding, and cell binding. Lead candidates were further subjected to in vivo biodistribution studies in mice bearing anaplastic thyroid cancer xenografts that express high levels of CD44v6. Additionally, antigen-dependent tumor uptake of the lead candidate was verified in additional xenograft models with varying levels of target expression. Interestingly, although only small differences were observed among the top antibody candidates in vitro, significant differences in tumor uptake and retention were uncovered in in vivo experiments. A high-affinity anti-CD44v6 lead drug candidate was identified, mAb UU-40, which exhibited favorable target binding properties and in vivo distribution. In conclusion, a panel of human anti-CD44v6 antibodies was successfully generated and characterized in this study. Through comprehensive evaluation, mAb UU-40 was identified as a promising lead candidate for future molecular radiotherapy of CD44v6-expressing cancers due to its high affinity, excellent target binding properties, and desirable in vivo distribution characteristics.

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Membranous CD44v6 is upregulated as an early event in colorectal cancer: Downregulation is associated with circulating tumor cells and poor prognosis

Cited by 6 publications

References 36 publications

CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas

CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas

CD44v6 expression in gastroenteropancreatic neuroendocrine neoplasms: Clinicopathological correlation and prognosis

Selection, characterization and in vivo evaluation of novel CD44v6-targeting antibodies for targeted molecular radiotherapy

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