Induction of gastric cancer cell adhesion through transforming growth factor-beta1-mediated peritoneal fibrosis

Lv, Zhi‐Dong; Di, Na; Liu, Funan; Du, Zongmin; Sun, Zhe; Li, Zhen; Ma, Xiaoyang; Wang, Zhenning; Xu, Hui

doi:10.1186/1756-9966-29-139

Cited by 38 publications

(35 citation statements)

References 29 publications

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“…TGF-β1 has been established to promote the expression of extracellular matrix (ECM) factors, including collagen, through Smad3 and the conversion of renal tubular epithelial cells into fibroblasts in the kidney via Smad2 (24). Regarding gastric cancer, TGF-β1 levels detected using an ELISA with peritoneal wash fluid samples are associated with peritoneal dissemination and depth of invasion (18). Furthermore, TGF-β1 induces the EMT of HPMCs in vitro and in vivo (25).…”

Section: Adhesion To the Peritoneummentioning

confidence: 99%

“…Subsequent previous studies have further demonstrated that TGF-β1 increases the expression of collagen I in rat peritoneal mesothelial cells via the c-Jun N-terminal kinase (JNK)/Smad3 signalling pathway, and of collagen III and fibronectin of HPMCs via Smad2 (26,27). Consequently, mesothelial cells stimulated by TGF-β1 promote peritoneal fibrosis via upregulating the expression of ECM proteins, including collagen I, collagen III and fibronectin (18). Cancer cells may anchor to the ECM via adhesion molecules; therefore peritoneal fibrosis mediated by TGF-β1 provides an effective 'soil' for dissemination.…”

Section: Adhesion To the Peritoneummentioning

confidence: 99%

“…Transmesothelial metastasis originates from the attachment of peritoneal-free cancer cells to the mesothelium (18). Human peritoneal mesothelial cells (HPMCs) have a vital role in this process.…”

Section: Adhesion To the Peritoneummentioning

confidence: 99%

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Mechanisms of peritoneal dissemination in gastric cancer (Review)

2017

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Abstract. Peritoneal dissemination is the most frequent metastatic pattern of gastric cancer, but the mechanisms underlying peritoneal dissemination are yet to be elucidated. Paget's 'seed and soil' hypothesis is recognized as the fundamental theory of metastasis. The 'seeding' theory proposes that the formation of peritoneal dissemination is a multistep process, including detachment from the primary tumour, transmigration and attachment to the distant peritoneum, invasion into subperitoneal tissue and proliferation with blood vascular neogenesis. In the present review, the progress of each step is discussed. Milky spots, as a lymphatic apparatus, are indicative of lymphatic orifices on the surface of the peritoneum. These stomata are open gates for peritoneal-free cancer cells to migrate into the submesothelial space. Therefore, milky spots provide suitable 'soil' for cancer cells to implant. Other theories have also been proposed to clarify the peritoneal dissemination process, including the transvessel metastasis theory, which suggests that the peritoneal metastasis of gastric cancer develops via a vascular network mediated by hypoxia inducible factor-1α.

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Section: Adhesion To the Peritoneummentioning

confidence: 99%

Section: Adhesion To the Peritoneummentioning

confidence: 99%

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Mechanisms of peritoneal dissemination in gastric cancer (Review)

2017

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“…In conclusion, the interaction of GC cells with the ECM appears to be of considerable importance in peritoneal metastasis as cancer cells that exfoliated into the abdominal cavity were found to attach initially to the mesothelial lining, followed by their invasion through the intercellular gaps of mesothelial cells (31). This study indicated that the adhesion of integrin α1-positive GC cells to the ECM is a critical process in peritoneal dissemination.…”

Section: Discussionmentioning

confidence: 82%

Role of integrin α1 subunits in gastric cancer patients with peritoneal dissemination

et al. 2011

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Abstract. The interaction between gastric cancer (GC) cells and the peritoneum is a critical event in peritoneal dissemination. The molecular mechanisms of this dissemination, however, remain unclear. Integrins are heterodimeric cell adhesion molecules consisting of α and β subunits that serve as adhesion receptors for extracellular matrix proteins and cellular ligands, and may participate in GC peritoneal dissemination. In this study, we isolated fresh GC cells from a patient with peritoneal metastasis and examined them for integrin expression and investigated the role of integrin α1 subunit molecules in GC. Five clones (KGC1C2, KGC1F3, KGC1H3, KGC1E8, KGC1G10) were established from the clinical GC sample and used in an in vitro adhesion model using a single cell culture method. Each clone was transplanted into the peritoneal cavity of SCID mice, where each clone formed tumors and caused conglutination of organs in the abdominal cavity. We analyzed the expression of integrin subunits for each clone by flow cytometry and found that the expression ratio of α1 subunits paired with β1 subunits was detected at higher levels than other subunits. To verify that anti-integrin α1 subunit (CD49a) antibody inhibits cell adhesion in an in vitro adhesion assay, each clone was treated with anti-CD49a antibody, which significantly inhibited cell adhesion compared to the untreated group. Characterization of α1 subunit expression in GC may be useful in optimizing treatments for different individuals. Having high metastatic abilities, these 5 new GC clones may be beneficial for analyzing integrin function in tumor metastasis.

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“…It can also regulate multiple cellular functions, including both inhibition and stimulation of proliferation, apoptosis and differentiation. Our previous study demonstrated that the TGF-β1 levels in peritoneal lavage fluid are significantly correlated with peritoneal metastasis and TNM stages of gastric cancer (9,10). In addition, TGF-β1 stimulates both the invasion and adhesion of gastric cancer cells to the peritoneum, thus resulting in an increase of the potential for peritoneal dissemination (11).…”

Section: Introductionmentioning

confidence: 99%

The cytotoxic effect of TGF-β1 on mesothelial cells via apoptosis in early peritoneal carcinomatosis

Yang

Wang

et al. 2012

Oncol Rep

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Abstract. Peritoneal dissemination is one of the main causes of death in gastric cancer patients. We have previously reported that gastric cancer cells can induce peritoneal apoptosis, lead to damage of peritoneum integrity, and therefore promote peritoneal metastasis. However, the soluble factors secreted by cancer cells to trigger the damaging cascade remain unclear. TGF-β1, a cytokine known for its capacity to induce proliferative and transformative changes of cells is found in significantly higher quantities correlated with peritoneal metastasis and TNM stages of gastric cancer. High levels of TGF-β1 in the subperitoneal milieu may affect the morphology and function of mesothelial cells, so that the resulting environment becomes favorable for peritoneal metastases. We observed apoptosis induced by TGF-β1 in mesothelial cells in peritoneal carcinomatosis. Knockdown of the Smad2 gene by siRNA silencing can partially inhibit these effects. TGF-β1 could upregulate the expressions of Bax and suppress Bcl-2 in mesothelial cells. We conclude that TGF-β1 could induce apoptosis of mesothelial cells, which involves the Smad2 signaling pathway in peritoneal carcinomatosis. Bcl-2 and Bax may contribute to this phenomenon.

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Induction of gastric cancer cell adhesion through transforming growth factor-beta1-mediated peritoneal fibrosis

Cited by 38 publications

References 29 publications

Mechanisms of peritoneal dissemination in gastric cancer (Review)

Mechanisms of peritoneal dissemination in gastric cancer (Review)

Role of integrin α1 subunits in gastric cancer patients with peritoneal dissemination

The cytotoxic effect of TGF-β1 on mesothelial cells via apoptosis in early peritoneal carcinomatosis

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