Molecular and phenotypic expression of decorin as modulator of angiogenesis in human potentially malignant oral lesions and oral squamous cell carcinomas

Nayak, Seema; Goel, Madhu Mati; Bhatia, Vikram; Chandra, S; Makker, Annu; Kumar, Sandeep; Agrawal, Siddharth; Mehrotra, Divya; Rath, Srikanta Kumar

doi:10.4103/0377-4929.120366

Cited by 16 publications

(10 citation statements)

References 22 publications

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“…To our knowledge, only one study has investigated the expression of the VEGFA gene in human oral squamous cell carcinoma . Our results indicate that aggressive oral squamous cell carcinomas exhibit high VEGFA transcript levels, and thus, VEGFA expression may be an important prognostic factor in this type of cancer.…”

Section: Discussionmentioning

confidence: 76%

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Elevated VEGFA mRNA levels in oral squamous cell carcinomas and tumor margins: a preliminary study

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Souza

et al. 2016

J Oral Pathology Medicine

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Section: Discussionmentioning

confidence: 76%

“…Few studies have investigated the expression of the VEGFA gene in OSCC and, to our knowledge, no study has evaluated its expression in tumor margins. In this study, we investigated the expression of the VEGFA gene and its immunohistochemical expression in oral squamous cell carcinomas (OSCC) and tumor margins.…”

Section: Introductionmentioning

confidence: 99%

Elevated VEGFA mRNA levels in oral squamous cell carcinomas and tumor margins: a preliminary study

Sales

Buim

Souza

et al. 2016

J Oral Pathology Medicine

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show abstract

“…Cawthorn and coworkers found that high decorin expression was associated with lymph node metastasis and poor clinical outcome in breast cancer; thus, decorin was proposed as an adverse prognostic and predictive biomarker [ 45 ]. Conversely, downregulation of decorin and lymph node metastasis independently predicted poor prognosis in oral squamous cell carcinomas [ 46 ]; DCN expression in osteosarcoma cells blocked their metastatic spread to the lungs [ 47 ]; and virus-mediated decorin delivery inhibited the growth of breast cancer and suppressed metastasis formation in various organs [ 48 , 49 , 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

The Protective Role of Decorin in Hepatic Metastasis of Colorectal Carcinoma

et al. 2020

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Decorin, the prototype member of the small leucine-rich proteoglycan gene family of extracellular matrix (ECM) proteins, acts as a powerful tumor suppressor by inducing the p21Waf1/Cip1 cyclin-dependent kinase inhibitor, as well as through its ability to directly bind and block the action of several tyrosine kinase receptors. Our previous studies suggested that the lack of decorin promotes hepatic carcinogenesis in mice. Based on this, we set out to investigate whether excess decorin may protect against the liver metastases of colon carcinoma. We also analyzed the effect of decorin in tissue microarrays of human colon carcinoma liver metastasis and examined whether the tumor cells can directly influence the decorin production of myofibroblasts. In humans, low levels of decorin in the liver facilitated the development of colon carcinoma metastases in proportion with more aggressive phenotypes, indicating a possible antitumor action of the proteoglycan. In vitro, colon carcinoma cells inhibited decorin expression in LX2 hepatic stellate cells. Moreover, liver-targeted decorin delivery in mice effectively attenuated metastasis formation of colon cancer. Overexpressed decorin reduced the activity of multiple receptor tyrosine kinases (RTKs) including the epidermal growth factor receptor (EGFR), an important player in colorectal cancer (CRC) pathogenesis. Downstream of that, we observed weakened signaling of ERK1/2, PLCγ, Akt/mTOR, STAT and c-Jun pathways, while p38 MAPK/MSK/CREB and AMPK were upregulated culminating in enhanced p53 function. In conclusion, decorin may effectively inhibit metastatic tumor formation in the liver.

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“…For instance, DCN exhibits antiangiogenic activities during cutaneous wound healing, while higher DCN expression was detected in human benign tumors vs. malignant vascular tumors (Jarvelainen et al, 2006;Salomaki et al, 2008). Meanwhile, impaired angiogenesis was found in the injured cornea of DCN-null mice (Schonherr et al, 2004), and repressed angiogenesis was also present in some tumors associated with reduced DCN expression (Nayak et al, 2013;Chui et al, 2014). These studies suggest that DCN can be either stimulatory or suppressive for angiogenesis, which may be related to the physiologic and pathologic conditions of tissues (Järveläinen et al, 2015).…”

Section: Angiogenesismentioning

confidence: 99%

Small Leucine-Rich Proteoglycans in Skin Wound Healing

2020

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Healing of cutaneous wounds is a complex and well-coordinated process requiring cooperation among multiple cells from different lineages and delicately orchestrated signaling transduction of a diversity of growth factors, cytokines, and extracellular matrix (ECM) at the wound site. Most skin wound healing in adults is imperfect, characterized by scar formation which results in significant functional and psychological sequelae. Thus, the reconstruction of the damaged skin to its original state is of concern to doctors and scientists. Beyond the traditional treatments such as corticosteroid injection and radiation therapy, several growth factors or cytokines-based anti-scarring products are being or have been tested in clinical trials to optimize skin wound healing. Unfortunately, all have been unsatisfactory to date. Currently, accumulating evidence suggests that the ECM not only functions as the structural component of the tissue but also actively modulates signal transduction and regulates cellular behaviors, and thus, ECM should be considered as an alternative target for wound management pharmacotherapy. Of particular interest are small leucine-rich proteoglycans (SLRPs), a group of the ECM, which exist in a wide range of connecting tissues, including the skin. This manuscript summarizes the most current knowledge of SLRPs regarding their spatial-temporal expression in the skin, as well as lessons learned from the genetically modified animal models simulating human skin pathologies. In this review, particular focus is given on the diverse roles of SLRP in skin wound healing, such as anti-inflammation, pro-angiogenesis, pro-migration, pro-contraction, and orchestrate transforming growth factor (TGF)b signal transduction, since cumulative investigations have indicated their therapeutic potential on reducing scar formation in cutaneous wounds. By conducting this review, we intend to gain insight into the potential application of SLRPs in cutaneous wound healing management which may pave the way for the development of a new generation of pharmaceuticals to benefit the patients suffering from skin wounds and their sequelae.

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Molecular and phenotypic expression of decorin as modulator of angiogenesis in human potentially malignant oral lesions and oral squamous cell carcinomas

Cited by 16 publications

References 22 publications

Elevated VEGFA mRNA levels in oral squamous cell carcinomas and tumor margins: a preliminary study

Elevated VEGFA mRNA levels in oral squamous cell carcinomas and tumor margins: a preliminary study

The Protective Role of Decorin in Hepatic Metastasis of Colorectal Carcinoma

Small Leucine-Rich Proteoglycans in Skin Wound Healing

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