Identification of a transforming growth factor beta-1 activator derived from a human gastric cancer cell line

Horimoto, Masayoshi; Kato, Junji; Takimoto, Rishu; Terui, Takeshi; Mogi, Yoshihiro; Niitsu, Yoshiro

doi:10.1038/bjc.1995.393

Cited by 34 publications

(18 citation statements)

References 25 publications

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“…They could be also attributed to the activated state of the HCs (1), or to the perturbed regulation of cytokine production in HCL, as we have previously demonstrated (5)(6)(7). Although the molecular mechanisms leading to activation of TGF-β1 in HCL are not completely understood, it is possible that HCs produce proteases that activate latent TGF-β in a manner similar to that of some neoplastic cells (54). In addition, direct contact between HCs and BMSCs may also induce activation of TGF-β1 through plasmin, as has been reported in cocultures of endothelial cells, pericytes, and smooth muscle cells (55).…”

Section: Discussionmentioning

confidence: 93%

TGF-β1 induces bone marrow reticulin fibrosis in hairy cell leukemia

Shehata¹,

Schwarzmeier²,

Hilgarth³

et al. 2004

J. Clin. Invest.

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Nonstandard abbreviations used: B cell chronic lymphocytic leukemia (B-CLL); bone marrow (BM); BM fibroblast (BMF); BM mononuclear cell (BMMC); BM plasma (BMP); BM stromal cell (BMSC); hairy cell (HC); HC leukemia (HCL); healthy donor (HD); peripheral blood plasma (PBP); procollagen type III aminoterminal propeptide (PIIINP). Conflict of interest:The authors have declared that no conflict of interest exists. IntroductionHairy cell leukemia (HCL) is a chronic lymphoproliferative disorder characterized by the presence of hairy cells (HCs) in peripheral blood, bone marrow (BM), and spleen and is invariably associated with a unique type of BM fibrosis (1-3). Although a rare disease (2% of adult leukemia), HCL represents an excellent model for cancer biotherapy (4) and for understanding the deregulation of cytokines and growth factors in human neoplasia (5-7). The fibrotic process and the associated structural abnormality in BM of HCL patients are mainly due to accumulation of fine argyrophilic reticulin fibers, although collagen fibers can be observed in the advanced stages of the disease (8-11). The composition of reticulin fibers in HCL is not well defined. In normal and fibrotic BM, the distribution of reticulin fibers is identical to that of type III collagen and its precursor, type III procollagen (12,13). Electron microscopic studies of human tissues revealed that reticulin fibers are individual collagen fibrils or small bundles of these fibrils embedded in the interfibrillar matrix of proteoglycans (14-16) and that they are composed mainly of type III collagen surrounding a core of type I collagen fibrils (17,18). In addition to reticulin fibrosis, it has been recently demonstrated that the glycoprotein fibronectin, which is produced and assembled by HCs, contributes to the fibrotic process in BM of HCL patients (19). This process was also found to be particularly enhanced by bFGF, which is endogenously produced by the HCs (20). Since reticulin and fibronectin fibers were found to represent different structures in myelofibrotic BM (21), it appears that BM fibrosis in HCL is a complex process that involves accumulation and assembly of collagenous ECM components (reticulin) (22) and noncollagenous ECM components (fibronectin).In BM, HCs are found in association with randomly dispersed fibroblastoid cells and are surrounded by reticulin fibers (9, 10, 23, 24). These fibroblastoid cells, which have been found in close association with collagen fibers, are the matrix-producing cells and are responsible for the synthesis of reticulin and collagen (9,(25)(26)(27)(28). Other studies confirmed the increase in the collagen fibrils in the intercellular space around the HCs but did not find evidence that HCs give rise to these fibrils (10). These studies also showed that HCs are not argyrophilic (29), suggesting that they may not be the direct source of reticulin fibers. Since no massive increase in fibroblast numbers is observed in the BM of HCL patients (10), the increased production of reticulin and ECM proteins mig...

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Section: Discussionmentioning

confidence: 93%

TGF-β1 induces bone marrow reticulin fibrosis in hairy cell leukemia

Shehata¹,

Schwarzmeier²,

Hilgarth³

et al. 2004

J. Clin. Invest.

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“…The TGF-β ligand is secreted as a latent dimer from the signaling cell [32]. Cotransfection experiments with LAP and mature TGF-β protein show that intracellular ligand processing and dimerization require the presence of LAP [33].…”

Section: Processing and Activationmentioning

confidence: 99%

The TGF-β Family: Signaling Pathways, Developmental Roles, and Tumor Suppressor Activities

Johnson

Newfeld

2002

The Scientific World JOURNAL

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Intercellular communication is a critical process for all multicellular organisms, and communication among cells is required for proper embryonic development and adult physiology. Members of the Transforming Growth Factor-β β β β (TGF-β β β β) family of secreted proteins communicate information between cells via a complex signaling pathway, and family members are capable of inducing a wide range of cellular responses. The purpose of this review is to provide the reader with a broad introduction to our current understanding of three aspects of the TGF-β β β β family. These are the molecular mechanisms utilized by TGF-β β β β signaling pathways, the developmental roles played by TGF-β β β β family members in a variety of species, and the growing list of cancers in which various TGF-β β β β signaling pathways display tumor suppressor activity.

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“…14 Cleavage of active TGF-␤ from the latent complex can be accomplished by several mechanisms including interaction with ␣v␤6 integrin 15 and proteolytic enzymes (such as plasmin), 12 thrombospondin, 16 and serine proteases produced by tumor cells. 17,18 Active TGF-␤ exerts its diverse biological effects by signaling through a heterodimeric receptor complex consisting of two types of TGF-␤ receptors, T␤RI and T␤ RII, with serine/threonine kinase activity. 19 Each subunit (T␤RI and II) is abundantly expressed at the surface of most cells as a homodimer.…”

Section: Structure and Molecular Mechanisms Of Action Of Tgf-␤mentioning

confidence: 99%

Effects of TGF-β on the immune system: implications for cancer immunotherapy

1999

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Transforming growth factor-␤ (TGF-␤) is a potent regulator of numerous processes including hematopoiesis, cell proliferation, differentiation and activation. TGF-␤ has pleiotropic and profound effects on the immune system and on hematologic malignancies, ie leukemia. It is the most potent immunosuppressor described to date. Evidence exists that the immunosuppressive potential of TGF-␤ is an important promoter of malignant cell growth. This is partly caused by TGF-␤-induced interference with the generation of tumor-specific cytotoxic T lymphocytes, but also by TGF-␤-induced promotion of angiogenesis and tumor stroma formation. Until now, significant clinical responses have not been achieved with the current cancer immunotherapeutic approaches. One of the possible explanations for this failure is immunosuppression induced by tumor-derived TGF-␤. Here, several strategies to counteract the immunosuppressive effects of TGF-␤ and the current limitations of these strategies will be discussed. Knowledge of the mechanisms by which TGF-␤ interferes with the development of an anti-tumor response and of the strategies to counteract these immunosuppressive activities is crucial to improve the current cancer immunotherapeutic approaches.

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Identification of a transforming growth factor beta-1 activator derived from a human gastric cancer cell line

Cited by 34 publications

References 25 publications

TGF-β1 induces bone marrow reticulin fibrosis in hairy cell leukemia

TGF-β1 induces bone marrow reticulin fibrosis in hairy cell leukemia

The TGF-β Family: Signaling Pathways, Developmental Roles, and Tumor Suppressor Activities

Effects of TGF-β on the immune system: implications for cancer immunotherapy

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