Serum nectin-2 levels are diagnostic and prognostic in patients with colorectal carcinoma

Karabulut, Mehmet; Günaldı, Meral; Alış, Halil; Afsar, Cu; Karabulut, Senem; Serilmez, Murat; Akarsu, Cevher; Seyit, Hakan; Aykan, Faruk

doi:10.1007/s12094-015-1348-1

Cited by 27 publications

(21 citation statements)

References 35 publications

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“…While the second CD226 ligand, nectin 2 or CD112, has been found to be overexpressed in many cancers including lymphoblastic leukemia and squamous cell carcinomas, one study also documents the presence of soluble nectin‐2 in sera of cancer patients. Baseline serum nectin‐2 levels were found to be elevated in patients with colorectal cancer, especially at the nonmetastatic levels . All these data show that the soluble isoforms of the immune checkpoint molecules can serve as important prognostic or diagnostic markers and also present with novel immunotherapeutic strategies in cancer.…”

Section: Immune Checkpoint Molecules: Regulating the Immune Response mentioning

confidence: 89%

“…Baseline serum nectin-2 levels were found to be elevated in patients with colorectal cancer, especially at the nonmetastatic levels. 143 All these data show that the soluble isoforms of the immune checkpoint molecules can serve as important prognostic or diagnostic markers and also present with novel immunotherapeutic strategies in cancer.…”

Section: Soluble Isoforms Of the Cd226/tigit: Cd155/cd112 Costimulamentioning

confidence: 99%

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Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

2019

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Background With the recent advances in the understanding of the interaction of the immune system with developing tumor, it has become imperative to consider the immunological parameters for both cancer diagnosis and disease prognosis. Additionally, in the era of emerging immunotherapeutic strategies in cancer, it is very important to follow the treatment outcome and also to predict the correct immunotherapeutic strategy in individual patients. There being enormous heterogeneity among tumors at different sites or between primary and metastatic tumors in the same individual, or interpatient heterogeneity, it is very important to study the tumor‐immune interaction in the tumor microenvironment and beyond. Importantly, molecular tools and markers identified for such studies must be suitable for monitoring in a noninvasive manner. Recent findings Recent studies have shown that the immune checkpoint molecules play a key role in the development and progression of tumors. In‐depth studies of these molecules have led to the development of most of the cancer immunotherapeutic reagents that are currently either in clinical use or under different phases of clinical trials. Interestingly, many of these cell surface molecules undergo alternative splicing to produce soluble isoforms, which can be tracked in the serum of patients. Conclusions Several studies demonstrate that the serum levels of these soluble isoforms could be used as noninvasive markers for cancer diagnosis and disease prognosis or to predict patient response to specific therapeutic strategies.

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Section: Immune Checkpoint Molecules: Regulating the Immune Response mentioning

confidence: 89%

Section: Soluble Isoforms Of the Cd226/tigit: Cd155/cd112 Costimulamentioning

confidence: 99%

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

2019

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“…DNAM-1 + GM NK-92 cells degranulated against all primary sarcoma explants as well as against the majority of the established cell lines, proving the potential of CD112 and CD155 as tumorspecific markers for targeted immunotherapies (Figures 3, 7). This, along with the absence of the degranulation response of NK cells against healthy donor PBMCs, showed that the use of DNAM-1 + GM NK-92 cells could be restricted/directed only to targets that had elevated CD112 and/or CD155 expression (Figures 2, 7), which is observed in tumors from various origins (65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83), including osteosarcomas (24).…”

Section: Discussionmentioning

confidence: 99%

Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D

et al. 2020

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Sayitoglu et al. Boosting NK Cell-Mediated Sarcoma Targeting cells was observed against the majority of tumor cell lines tested. In conclusion, DNAM-1 or NKG2D over-expression elicited a dynamic increase in NK cell degranulation against all sarcoma explants and cancer cell lines tested, including those that failed to induce a notable response in WT NK-92 cells. These results support the broad therapeutic potential of DNAM-1 + or NKG2D + GM NK-92 cells and GM human NK cells for the treatment of sarcomas and other malignancies.

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“…So far, although only few investigations exist, the involvement of Nectin‐2 in tumor pathogenesis has been described for different tumor entities, such as breast and ovarian cancer, but also for gallbladder, colorectal or pancreatic cancer . In some of these studies, high expression of Nectin‐2 was associated with high malignancy, advanced tumor stage, poor differentiation, fast progression and poor outcome/prognosis . At the same time, inhibition of Nectin‐2 was followed by ceasing proliferation of tumor cells in cell culture.…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21] In some of these studies, high expression of Nectin-2 was associated with high malignancy, advanced tumor stage, poor differentiation, fast progression and poor outcome/prognosis. [20][21][22] At the same time, inhibition of Nectin-2 was followed by ceasing proliferation of tumor cells in cell culture. These studies indicate the high potential of Nectin-2 as a target for antibody therapeutics.…”

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confidence: 99%

Nectin‐2 in ovarian cancer: How is it expressed and what might be its functional role?

et al. 2019

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Nectin‐2 is an adhesion molecule that has been reported to play a role in tumor growth, metastasis and tumor angiogenesis. Herein, we investigated Nectin‐2 in ovarian cancer patients and in cell culture. Tumor as well as peritoneal biopsies of 60 ovarian cancer patients and 22 controls were dual stained for Nectin‐2 and CD 31 using immunohistochemistry. Gene expression of Nectin‐2 was quantified by real‐time PCR and differences analyzed in relation to various tumor characteristics. In the serum of patients, vascular endothelial growth factor ( VEGF ) was quantified by ELISA . Effect of VEGF on Nectin‐2 expression as well as permeability was investigated in HUVEC . In tumor biopsies, Nectin‐2 protein was mainly localized in tumor cells, whereas in peritoneal biopsies, clear colocalization was found in the vasculature. T3 patients had a significantly higher percentage of positive lymph nodes and this correlated with survival. Nectin‐2 was significantly upregulated in tumor biopsies in patients with lymph node metastasis and with residual tumor >1 cm after surgery. Nectin‐2 expression was significantly suppressed in the peritoneal endothelium of patients associated with significantly increased VEGF serum levels. In cell culture, VEGF stimulation led to a significant downregulation of Nectin‐2 which was reversed by VEGF ‐inhibition. In addition, Nectin‐2 knockdown in endothelial cells was associated with significantly increased endothelial permeability. Nectin‐2 expression in ovarian cancer may support tumor cell adhesion, leading to growth and lymph node metastasis. In addition, VEGF ‐induced Nectin‐2 suppression in peritoneal endothelium may support an increase in vascular permeability leading to ascites production.

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Serum nectin-2 levels are diagnostic and prognostic in patients with colorectal carcinoma

Abstract: Serum levels of nectin-2 may have diagnostic roles for CRC patients. Moreover, our study results show the prognostic role of nectin-2 in non-metastatic group patients.

Cited by 27 publications

References 35 publications

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D

Nectin‐2 in ovarian cancer: How is it expressed and what might be its functional role?

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