Tumor‑associated macrophages recruited by periostin in intrahepatic cholangiocarcinoma stem cells

Zeng, Jiehong; Liu, Zhengkai; Sun, Shi; Xie, Jianhong; Cao, Li; Lv, Pin; Nie, Sheng; Bao, Zhenan; Xie, Bowen; Peng, Siyuan; Jiang, Bo

doi:10.3892/ol.2018.8372

Cited by 25 publications

(21 citation statements)

References 30 publications

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“…Knockdown of integrin α5 reduced CCA proliferation and invasion. 82 Recent data indicate that iCCA cells are also able to secrete periostin and to recruit TAM, 83 similar to what is described for glioblastoma, where periostin generated by the cancer stem cells recruited TAM to promote tumor growth. 84 In iCCA, the malignant potential stimulated by periostin was mediated by induction of EMT changes instigating cell proliferation, migration, and invasion, as well as enhancing chemoresistance to gemcitabine; interestingly, these proinvasive functions were all inhibited by knockdown of periostin in iCCA cells.…”

Section: Altered Composition Of Ecm In Ccamentioning

confidence: 56%

Liver Matrix in Benign and Malignant Biliary Tract Disease

et al. 2020

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The extracellular matrix is a highly reactive scaffold formed by a wide array of multifunctional molecules, encompassing collagens and noncollagenous glycoproteins, proteoglycans, glycosaminoglycans, and polysaccharides. Besides outlining the tissue borders, the extracellular matrix profoundly regulates the behavior of resident cells by transducing mechanical signals, and by integrating multiple cues derived from the microenvironment. Evidence is mounting that changes in the biostructure of the extracellular matrix are instrumental for biliary repair. Following biliary damage and eventually, malignant transformation, the extracellular matrix undergoes several quantitative and qualitative modifications, which direct interactions among hepatic progenitor cells, reactive ductular cells, activated myofibroblasts and macrophages, to generate the ductular reaction. Herein, we will give an overview of the main molecular factors contributing to extracellular matrix remodeling in cholangiopathies. Then, we will discuss the structural alterations in terms of biochemical composition and physical stiffness featuring the “desmoplastic matrix” of cholangiocarcinoma along with their pro-oncogenic effects.

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Section: Altered Composition Of Ecm In Ccamentioning

confidence: 56%

Liver Matrix in Benign and Malignant Biliary Tract Disease

et al. 2020

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“…Among the significant over-expressed proteins identified in iCCA (i.e. : POSTN, COL3A1, COL12A1), the overexpression of periostin has been extensively demonstrated to promote cholangiocarcinogenesis [9, 10, 27, 28]. Since it has been reported that, in various invasive cancers, the overexpression of COL3A1 promotes tumor progression and confers poor prognosis, we therefore investigated the possible effects of COL3A1 in modifying iCCA cells behaviour.…”

Section: Resultsmentioning

confidence: 99%

Matrisome analysis of intrahepatic cholangiocarcinoma unveils a peculiar cancer-associated extracellular matrix structure

et al. 2019

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BackgroundIntrahepatic cholangiocarcinoma (iCCA) is a malignancy that arises from the intrahepatic biliary tree, showing high mortality rates due to its late clinical presentation and limited treatment options. iCCA is characterized by a dense, reactive desmoplastic stroma marked by a dramatic accumulation of extracellular matrix (ECM). Although recent results strongly suggest a relationship between increasing desmoplastic stroma and the enhanced malignant behaviour of iCCA, the importance of ECM proteins in the pathogenesis of iCCA still have to be addressed.MethodsiCCA ECM fibrillar structural organization was characterized by histological analysis. ECM proteome profiles from decellularized iCCA and surrounding noncancerous tissues were analysed by nLC coupled to MALDI-TOF/TOF analysis.ResultsiCCA tissues displayed high levels of collagen fibers and low abundance of reticular and elastic fibers, suggesting stiffness and loss of polarity. The ECM proteome profiles of iCCA samples, when compared to those obtained from the surrounding noncancerous tissues showed a dismantling of the basement membrane, a reduced angiogenesis and a downregulation of oncosuppressive activity. In particular, we focused on the effects of the overexpression of collagen type III alpha 1 chain (COL3A1) in iCCA, thus providing evidences that COL3A1 promotes iCCA cells migration and is a component of tumor-associated aligned collagen.ConclusionsOverall, this study contributes to the understanding of molecular basis underlying desmoplasia in iCCA and indicates the type III collagen as a promising therapeutic target.

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“…Furthermore, it was reported that periostin, a disulfide-linked cell adhesion protein, plays an important role in tumor progression [120]. Recently, it was proven that periostin is secreted by CD44 + iCCA stem cells, and may serve as a chemoattractant for M2 TAM recruitment [121].…”

Section: Tumor Microenvironment (Tme)mentioning

confidence: 99%

Role of Cancer Stem Cells in Cholangiocarcinoma and Therapeutic Implications

Chu

2019

IJMS

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Cholangiocarcinoma (CCA) is the second most common type of liver cancer, and is highly aggressive with very poor prognosis. CCA is classified into intrahepatic cholangiocarcinoma (iCCA) and extra-hepatic cholangiocarcinoma (eCCA), which is further stratified into perihilar (pCCA) and distal (dCCA). Cancer stem cells (CSCs) are a subpopulation of cancer cells capable of tumor initiation and malignant growth, and are also responsible for chemoresistance. Thus, CSCs play an important role in CCA carcinogenesis. Surface markers such as CD133, CD24, CD44, EpCAM, Sox2, CD49f, and CD117 are important for identifying and isolating CCA CSCs. CSCs are present in the tumor microenvironment (TME), termed ‘CSC niche’, where cellular components and soluble factors interact to promote tumor initiation. Epithelial-to-mesenchymal transition (EMT) is another important mechanism underlying carcinogenesis, involved in the invasiveness, metastasis and chemoresistance of cancer. It has been demonstrated that EMT plays a critical role in generating CSCs. Therapies targeting the surface markers and signaling pathways of CCA CSCs, proteins involved in TME, and immune checkpoint proteins are currently under investigation. Therefore, this review focuses on recent studies on the roles of CSCs in CCA; the possible therapeutic strategies targeting CSCs of CCA are also discussed.

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Tumor‑associated macrophages recruited by periostin in intrahepatic cholangiocarcinoma stem cells

Cited by 25 publications

References 30 publications

Liver Matrix in Benign and Malignant Biliary Tract Disease

Liver Matrix in Benign and Malignant Biliary Tract Disease

Matrisome analysis of intrahepatic cholangiocarcinoma unveils a peculiar cancer-associated extracellular matrix structure

Role of Cancer Stem Cells in Cholangiocarcinoma and Therapeutic Implications

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