Matrix Gla protein in tumoral pathology

Gheorghe, Simona; Crăciun, Alexandra

doi:10.15386/cjmed-579

Cited by 24 publications

(31 citation statements)

References 25 publications

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“…Among the 17 Gla-protein members, Periostin (POSTN) and Matrix Gla-Protein (MGP) are known to affect ECM crosslinking and various cellular behaviors, such as migration, adhesion and proliferation in epithelial, endothelial, fibroblast, osteoblast and myocyte cells (23)(24)(25)(26)(27). POSTN is expressed in osteoblast, mesangial, fibroblast, mesenchymal and vascular smooth muscle cells (22), while MGP is typically secreted and localized in the surrounding ECM of chondrocytes or endothelial cells (28).…”

Section: Introductionmentioning

confidence: 99%

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

et al. 2020

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The extracellular matrix (ECM) surrounding cells is indispensable for regulating their behavior. The dynamics of ECM signaling are tightly controlled throughout growth and development. During tissue remodeling, matricellular proteins (MCPs) are secreted into the ECM. These factors do not serve classical structural roles, but rather regulate matrix proteins and cell-matrix interactions to influence normal cellular functions. In the tumor microenvironment, it is becoming increasingly clear that aberrantly expressed MCPs can support multiple hallmarks of carcinogenesis by interacting with various cellular components that are coupled to an array of downstream signals. Moreover, MCPs also reorganize the biomechanical properties of the ECM to accommodate metastasis and tumor colonization. This realization is stimulating new research on MCPs as reliable and accessible biomarkers in cancer, as well as effective and selective therapeutic targets. Research.

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Section: Introductionmentioning

confidence: 99%

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

et al. 2020

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“…Further investigation demonstrated that MGP had a wider range of activities, which were dependent of the phosphorylation-carboxylation status, protein expression and variants. Recent studies showed that MGP has a role in tumor angiogenesis by increasing vascular endothelial growth factor gene expression [51][52][53]. Recently, MGP was reported to be upregulated in a variety of tumors, including ovarian, breast, urogenital and skin cancer.…”

Section: Discussionmentioning

confidence: 99%

“…We suggest that the discrepancy between the tissue regions analyzed by DNA microarray and those subjected to immunohistochemical analysis led to this result. The relatively low immunoreactivity scores of GPNMB and MGP may be attributed to the timing of degradation and wash-out of these proteins from the tissue [53].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive genomic analysis contrasting primary colorectal cancer and matched liver metastases: a retrospective study

Shiomi

Kusuhara

Sugino

et al. 2020

Preprint

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(Background)Recent studies have revealed that colorectal cancer (CRC) displays intratumor genetic heterogeneity, and the cancer microenvironment play an important role in the proliferation, invasion, and metastasis of CRC.(Methods)We performed genomic analysis on 22 paired patients with primary CRC and synchronous colorectal liver metastasis (CRLM) using whole-exome sequencing, cancer gene panels, and microarray gene expression profiling. In addition, immunohistochemical analysis was used to confirm the protein expression of genes identified as highly expressed in CRLM by DNA microarray analysis.(Results)A total of 22 paired patients were enrolled in this study, including 13 (59.1%) colon and 9 (40.9%) rectal cancer patients. All patients had synchronous liver metastasis and did not have any other extrahepatic metastases. We identified 11 probes (10 genes) that were highly expressed in CRLM compared to CRC, from 36022 probes obtained from primary CRC, CRLM, and normal liver tissues, using gene expression analysis with DNA microarray. Of the 11 probes (10 genes), 5 genes classified as encoding “matricellular proteins” (osteopontin, periostin, thrombospondin-2, MGP, and GPNMB) were selected for immunohistochemical analysis.Osteopontin was strongly expressed in CRLM (6 of 22 cases: 27.3%) but not in CRC (0 of 22: 0%; p=0.02). Periostin also showed strong immunoreactivity in CRLM (17 of 22: 68.2%) compared to 7 of 22 (31.8%) in CRC (p=0.006). Thrombospondin-2 showed strong immunoreactivity both in CRC and CRLM (54.5% in CRC, 45.5% in CRLM; p=0.55). GPNMB and MGP were rarely positive for both CRC and CRLM. A comparison of immunoreactive positive factors for these 5 genes revealed the complexities of gene expression in CRLM. Of the cases, 16 (72.7%) CRC revealed zero or only one positive immunoreactivity. On the other hand, CRLM revealed more frequent multiple immunoreactivity; 16 cases (72.7%) shared 2 or more factors, which was statistically more frequent in CRLM than in CRC (p=0.007).(Conclusions)This study revealed the genomic heterogeneity between paired primary CRC and CRLM in terms of cancer cell microenvironment. This finding will lead to new diagnostic and therapeutic targets in the era of genome-guided personalized cancer treatment.(Trial registration)This study was retrospectively registered.

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“…Previous studies showed aberrant expression of MGP in various types of cancers and exert dual biological functions, acting as an oncogene or tumor‐suppressor, by regulating the expression of different target genes (Gheorghe and Crăciun, 2016). However, the regulatory role of MGP in tumorigenesis is still controversial.…”

Section: Introductionmentioning

confidence: 99%

Intracellular matrix Gla protein promotes tumor progression by activating JAK2/STAT5 signaling in gastric cancer

Wang

Chen

et al. 2020

Molecular Oncology

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Matrix Gla protein (MGP) has been widely reported as an extracellular matrix protein with abnormal expression in various types of cancer. However, the function of intracellular MGP in gastric cancer (GC) cells remains largely unknown. Here, we demonstrated aberrantly high expression of intracellular MGP in GC as compared to adjacent normal tissues by immunohistochemistry. Moreover, The Cancer Genome Atlas (TCGA) dataset analysis suggested a positive correlation between MGP overexpression and unfavorable prognosis. MGP silencing reduced cell proliferation, migration, invasion, and survival in GC cell lines. Gene set enrichment analysis of TCGA dataset indicated significant enrichment of the IL2-STAT5 signaling in MGP-high GC patients. Immunofluorescence staining and immunoprecipitation showed that MGP binds to p-STAT5 in the nuclei of GC cells. Furthermore, ChIP-qPCR and luciferase reporter assays indicated that MGP acts as a transcriptional co-activator through the enhancement of STAT5 binding to target gene promoters. Use of STAT5 inhibitor revealed that the oncogenic functions of intracellular MGP mainly depend on the JAK2/STAT5 signaling pathway. Taken together, our results indicate that intracellular MGP promotes proliferation and survival of GC cells by acting as a transcriptional co-activator of STAT5. The detected aberrant, high MGP expression in GC tissues highlights MGP as a potential new prognostic biomarker in patients with GC.

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Matrix Gla protein in tumoral pathology

Cited by 24 publications

References 25 publications

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

Comprehensive genomic analysis contrasting primary colorectal cancer and matched liver metastases: a retrospective study

Intracellular matrix Gla protein promotes tumor progression by activating JAK2/STAT5 signaling in gastric cancer

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