Synthesis and degradation of basement membranes and extracellular matrix and their regulation by TGF-β in invasive carcinomas (Review)

Hagedorn, Hjalmar; Bachmeier, Beatrice E.; Nerlich, Andreas

doi:10.3892/ijo.18.4.669

Cited by 57 publications

(57 citation statements)

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“…Among them, MMP2 and MMP9 belong to the gelatinase family and contribute to the degradation of extracellular substrates such as collagen type IV, the main component of the basement membrane (4,(13)(14)(15) comparing the expression levels between the primary and the metastatic regions of OSCC. In the present study, we attempted to evaluate the expression profiles of MMP2 and MMP9.…”

Section: Discussionmentioning

confidence: 99%

Comparison of MMP2 and MMP9 expression levels between primary and metastatic regions of oral squamous cell carcinoma

et al. 2016

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Matrix metalloproteinases (MMPs)and tumor-associated macrophages (TAMs) play important roles in tumor growth. The present study investigated the expression levels of MMP2 and MMP9 in relation to the distribution of TAMs in the primary and metastatic regions of oral squamous cell carcinoma. Twenty-nine cases of oral squamous cell carcinoma (OSCC) with regional lymph node metastasis were selected from available documents in the archives of the Department of Pathology, Nihon University School of Dentistry. Four-micrometerthick sections were prepared from the primary and metastatic regions. Each section was subjected to immunohistochemical staining using anti-MMP2, anti-MMP9, and anti-CD68 antibodies. The distribution and localization of MMPs and TAMs were compared between primary and metastatic regions. The expression levels of both MMPs were higher in the metastatic regions of lingual and gingival cancers. Statistically significant differences were observed in both T1 and T2 cases. In contrast to the higher expression of MMPs in metastatic regions, a higher number of TAMs were distributed in the primary regions. From these results, MMP expression levels and the numbers of TAMs were expected to have an inverse relationship between the primary and metastatic regions of OSCC. (J Oral Sci 58, 59-65, 2016)

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Section: Discussionmentioning

confidence: 99%

Comparison of MMP2 and MMP9 expression levels between primary and metastatic regions of oral squamous cell carcinoma

et al. 2016

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“…These transcription factors have been shown to interact and induce expression of the npg VEGF [70]. Additionally, TGFb can regulate the expression, secretion, and activity of matrix metalloproteases MMP-2 and MMP-9, and downregulate the expression of the protease inhibitor TIMP in the tumor and endothelial cells [71,72]. Through these metalloprotease activities, TGFb can enhance the migratory and invasive properties of endothelial cells required for angiogenesis.…”

Section: Angiogenesismentioning

confidence: 99%

Roles of TGFβ in metastasis

2008

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The TGFβ signaling pathway is conserved from flies to humans and has been shown to regulate such diverse processes as cell proliferation, differentiation, motility, adhesion, organization, and programmed cell death. Both in vitro and in vivo experiments suggest that TGFβ can utilize these varied programs to promote cancer metastasis through its effects on the tumor microenvironment, enhanced invasive properties, and inhibition of immune cell function. Recent clinical evidence demonstrating a link between TGFβ signaling and cancer progression is fostering interest in this signaling pathway as a therapeutic target. Anti-TGFβ therapies are currently being developed and tested in preclinical studies. However, targeting TGFβ carries a substantial risk as this pathway is implicated in multiple homeostatic processes and is also known to have tumor-suppressor functions. Additionally, clinical and experimental results show that TGFβ has diverse and often conflicting roles in tumor progression even within the same tumor types. The development of TGFβ inhibitors for clinical use will require a deeper understanding of TGFβ signaling, its consequences, and the contexts in which it acts.

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“…TGF-␤1 inhibits the proliferation of a wide range of cells, including those of epithelial, endothelial, and neuronal origin, as well as those of the immune system, while it stimulates the growth of fibroblasts (for a review, see J Massagué et al, 2000). In addition to the effects of TGF-␤1 on cellular growth, TGF-␤1 can inhibit the differentiation of certain mesodermal cells, induce the differentiation of others, regulate the production and deposition of extracellular matrix and adhesion proteins, and affect the migration of several TGF-␤1-responsive cell types (for reviews, see Smith, 1996;Hagedorn et al, 2001). Although much of the mechanism for intracellular signaling of TGF-␤ has been elucidated, the whole spectrum of target genes that contribute to the induction and/or maintenance of the specific responses resulting from TGF-␤1 and that may be important in determining the ultimate outcome of TGF-␤1 responsiveness, continues to be determined.…”

Section: Introductionmentioning

confidence: 99%

Expression of differentially expressed nucleolar transforming growth factor‐β1 target (DENTT) in adult mouse tissues

Martı́nez

Ozbun

Angdisen

et al. 2002

Developmental Dynamics

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Differentially expressed nucleolar TGF-␤1 target (DENTT) is a novel member of the TSPY/TSPY-L/SET/NAP-1 (TTSN) superfamily that we have previously identified in human lung cancer cells. Here, we have investigated the expression of this protein in the adult mouse. By Western analysis, DENTT is highly expressed in the pituitary gland and moderately in the adrenals, brain, testis, and ovary. Immunohistochemical staining analysis for DENTT showed differential cytoplasmic and nuclear staining patterns in several cell types. The pituitary gland showed the highest level of immunostaining for DENTT, with strong cytoplasmic immunoreactivity in the anterior lobe, moderate levels in the posterior lobe, and a few cells showing nuclear staining in the intermediate lobe. In contrast, the intermediate lobe of the pituitary showed intense cytoplasmic staining for TGF-␤1. Nuclear and cytoplasmic staining for DENTT was present in the islets of Langerhans in the pancreas. Cytoplasmic staining for DENTT was particularly intense in the cortex of the adrenal gland, whereas the medulla showed weak nuclear staining. In the nervous system, the choroid plexus showed the highest immunoreactivity, with cortical motoneurons and Purkinje cells having relatively high levels of staining for DENTT as well. DENTT immunoreactivity was found in Leydig interstitial cells, Sertoli cells, and primary spermatocytes in the testis. In the female reproductive system, DENTT immunoreactivity was present in oocytes, thecal cells, and corpora lutea. The bronchial epithelium of the lung showed moderate levels of staining for DENTT localized to the cell nucleus. Additionally, three rodent pituitary cell lines (AtT20, GH3, and ␣T3-1, representing corticotropes, lactotropes, and gonadotropes, respectively) showed expression of DENTT. Addition of TGF-␤1 or serum to AtT20 cells increased DENTT protein production by 4 hr and, after reaching maximal levels at 2.4-fold above basal level by 8 hr, decreased, whereas no more than a 1.5-fold increase in DENTT protein occurred in GH3 or ␣T3-1 cells. Transient transfection studies showed that ectopic DENTT expression significantly increased the level of p3TP-Lux re-

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Synthesis and degradation of basement membranes and extracellular matrix and their regulation by TGF-β in invasive carcinomas (Review)

Cited by 57 publications

References 0 publications

Comparison of MMP2 and MMP9 expression levels between primary and metastatic regions of oral squamous cell carcinoma

Comparison of MMP2 and MMP9 expression levels between primary and metastatic regions of oral squamous cell carcinoma

Roles of TGFβ in metastasis

Expression of differentially expressed nucleolar transforming growth factor‐β1 target (DENTT) in adult mouse tissues

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