YKL-40/CHI3L1 drives inflammation on the road of tumor progression

Libreros, Stephania; Iragavarapu-Charyulu, Vijaya

doi:10.1189/jlb.3vmr0415-142r

Cited by 84 publications

(66 citation statements)

References 65 publications

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“…Chitinase 3-like 1 (CHI3L1) is a member of the glycosyl hydrolase 18 family. CHI3L1 is considered to serve a role in the process of inflammation and tissue remodeling (34). A previous study demonstrated the association of high serum CHI3L1 expression level with poor patient prognosis and short survival time in human solid tumors, including lung cancer and liver cancer (35).…”

Section: Discussionmentioning

confidence: 99%

iTRAQ‑based quantitative proteomic analysis and bioinformatics study of proteins in retinoblastoma

et al. 2017

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Abstract. The aim of the present study was to analyze proteins in the aqueous humor (AH) of patients' retinoblastoma (RB), and investigate their potential role in RB using the comparative proteomic technique of isobaric tags for relative and absolute quantitation (iTRAQ) coupled with offline two-dimensional liquid chromatography-tandem mass spectrometry. A total of 0.1 ml AH was collected from 10 children with RB (mean age, 3.8 years; range, 2-5 years) and patients with senile cataracts (mean age, 70.4 years; range, 65-79 years), which was used as the control. iTRAQ was used to analyze proteins in the AH of patients and controls. Proteins with a fold change of >1.20 or <0.83 were considered to be significantly differentially expressed (with corrected P<0.05). The identified proteins were subjected to subsequent gene ontology (GO) analysis using the DAVID database. A total of 83 proteins that were expressed differently between the controls and patients' AH samples were identified using iTRAQ analysis. Of these proteins, 44 were upregulated and 39 were downregulated. On the basis of biological processes in GO, the identified proteins were primarily involved in glycoprotein, amyloid acute-inflammatory and defensive responses. Among these proteins, pigment epithelium-derived factor serves a potential role in the treatment of RB, and stimulated by retinoic acid 6 may serve as a potential protein involved in RB development. To the best of our knowledge, the present study is the first to identify 83 proteins associated with RB using iTRAQ technology. The results of the present study will aid in furthering the understanding of RB and developing novel therapy targets in the future.

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Section: Discussionmentioning

confidence: 99%

iTRAQ‑based quantitative proteomic analysis and bioinformatics study of proteins in retinoblastoma

et al. 2017

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“…Accumulating data reveals that CLPs play a role in the progression of different types of cancer. Elevated levels of circulating YKL-40 are related to poor outcome or short diseasefree survival in glioblastoma, melanoma, ovarian, breast, colon, lung, and prostate cancers in humans (52,(84)(85)(86)(87)(88)(89)(90)(91)(92). Moreover, in breast cancer, elevated serum levels of YKL-40 have been used as a prognostic biomarker (84).…”

Section: Chitinase-like Proteins In Cancermentioning

confidence: 99%

YKL-39 as a Potential New Target for Anti-Angiogenic Therapy in Cancer

2020

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YKL-39 belongs to the evolutionarily conserved family of Glyco_18-containing proteins composed of chitinases and chitinase-like proteins. Chitinase-like proteins (CLPs) are secreted lectins that lack hydrolytic activity due to the amino acid substitutions in their catalytic domain and combine the functions of cytokines and growth factors. One of the major cellular sources that produce CLPs in various pathologies, including cancer, are macrophages. Monocytes recruited to the tumor site and programmed by tumor cells differentiate into tumor-associated macrophages (TAMs), which are the primary source of pro-angiogenic factors. Tumor angiogenesis is a crucial process for supplying rapidly growing tumors with essential nutrients and oxygen. We recently determined that YKL-39 is produced by tumor-associated macrophages in breast cancer. YKL-39 acts as a strong chemotactic factor for monocytes and stimulates angiogenesis. Chemotherapy is a common strategy to reduce tumor size and aggressiveness before surgical intervention, but chemoresistance, resulting in the relapse of tumors, is a common clinical problem that is critical for survival in cancer patients. Accumulating evidence indicates that TAMs are essential regulators of chemoresistance. We have recently found that elevated levels of YKL-39 expression are indicative of the efficiency of the metastatic process in patients who undergo neoadjuvant chemotherapy. We suggest YKL-39 as a new target for anti-angiogenic therapy that can be combined with neoadjuvant chemotherapy to reduce chemoresistance and inhibit metastasis in breast cancer patients.

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“…For example, YKL-40 gene silence such as shRNA can abrogate tumor growth and angiogenesis [2]. Dr. V. Iragavarapu-Charyulu group employed chitin, a YKL-40 binding ligand, in breast cancer transplanted mice and interestingly found that chitin can protect cancer cells from lung metastasis [5], supporting the notion that competitive binding at YKL-40 heparin-binding motif is an alternative approach to attenuating YKL-40-mediated cancer dissemination. To provide immunotherapeutic value, we recently created a mouse-derived neutralizing antibody against YKL-40 that displays the ability to bind YKL-40 functional domain, thus ablating tumor angiogenesis [4].…”

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confidence: 94%

Secreted glycoprotein YKL-40: A potential cancer biomarker and therapeutic target

Shao¹

2018

Integr Cancer Sci Therap

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Over the past two decades, we have substantially gained knowledge about the secreted glycoprotein YKL-40, also named chitinase 3-like 1 (Chi3L1) in many aspects of research field arranging from basic molecular biology to clinical applications. In 1990's, YKL-40 was found to be expressed by cells in a variety of normal tissues including chondrocytes and synoviocytes in bone, vascular smooth muscle cells in blood vessels, and macrophages in the immune system. Thus, its biological and physiological activity is associated with bone-related cell proliferation, vascular cell migration, and macrophage differentiation. Given the evidence that YKL-40 was initially identified from cultured medium of an osteosarcoma line MG-63 cells, it was not unexpected that abundance of subsequent research interest had focused on the aberrant expression of YKL-40 in many cancers and other human disorders. Elevated serum levels of YKL-40 were demonstrated in patients with breast cancer, colorectal cancer, ovarian cancer, leukemia, lymphoma, and glioblastoma. Furthermore, increased YKL-40 serum levels in these cancer patients were correlated with reduced cancer survival and/or cancer metastases [1]. Therefore, YKL-40 has been pointed to be a diagnostic and prognostic biomarker for patients with a broad type of cancers.Since YKL-40 is a "false" chitinase that lacks hydrolytic activity, even YKL-40 is able to bind to chitin-like oligosaccharides; its pathophysiological activity and molecular mechanisms are not fully understood until recent several years. YKL-40 binds to heparin sulfate chains distributed at ectodomain of membrane protein syndecan-1 [2]. In addition, Dr. J. Elias group has revealed that YKL-40 specifically binds to the membrane receptor IL-13R2α [3]. A number of research labs including us have reported that intracellular signaling pathways for YKL-40 are associated with activation of FAK-MAPK and PI3K/ Akt, which mediate tumor angiogenesis and tumor cell invasiveness induced by YKL-40. Furthermore, we have recently added large effort to demonstrate that a heparin-binding motif containing a cluster of arginine and lysine residues at C terminus of YKL-40 is the functional domain that commits YKL-40 to driving angiogenesis [4]. Altogether, these findings have led us to better understand the molecular mechanisms that mediate YKL-40 pathologic activity in multiple human cancers.Albeit these mechanistic insights have offered a number of therapeutic opportunities potential to block YKL-40 function, clinical intervention directly targeting YKL-40 in patients remains to be investigated. It is notable that there are a few pre-clinical trials reported to successfully inhibit YKL-40. For example, YKL-40 gene silence such as shRNA can abrogate tumor growth and angiogenesis [2]. Dr. V. Iragavarapu-Charyulu group employed chitin, a YKL-40 binding ligand, in breast cancer transplanted mice and interestingly found that chitin can protect cancer cells from lung metastasis [5], supporting the notion that competitive binding at YKL-40 heparin-b...

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YKL-40/CHI3L1 drives inflammation on the road of tumor progression

Cited by 84 publications

References 65 publications

iTRAQ‑based quantitative proteomic analysis and bioinformatics study of proteins in retinoblastoma

iTRAQ‑based quantitative proteomic analysis and bioinformatics study of proteins in retinoblastoma

YKL-39 as a Potential New Target for Anti-Angiogenic Therapy in Cancer

Secreted glycoprotein YKL-40: A potential cancer biomarker and therapeutic target

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