The SPARC protein: an overview of its role in lung cancer and pulmonary fibrosis and its potential role in chronic airways disease

Wong, Sharon L.; Sukkar, Maria B.

doi:10.1111/bph.13653

Cited by 80 publications

(66 citation statements)

References 100 publications

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“…It is a member of a family of proteins that modulate interactions between cells and their environment by regulating growth factor signaling and extracellular matrix assembly and deposition. 62 SPARC functions as both a secreted glycoprotein and an intracellular and membraneassociated protein that regulates cellular apoptotic pathways. 62 It shows increased expression in 62 Interestingly, this fusion was found in a case occurring in the tendon of the hand (case 15).…”

Section: Discussionmentioning

confidence: 99%

USP6 activation in nodular fasciitis by promoter-swapping gene fusions

et al. 2017

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Nodular fasciitis is a self-limited myofibroblastic lesion that can be misdiagnosed as a sarcoma as a result of its rapid growth, cellularity, and sometimes prominent mitotic activity. A recurrent translocation t(17;22) has been identified in nodular fasciitis, fusing the coding region of USP6 to the promoter region of MYH9, and resulting in increased USP6 expression. A subset of cases show USP6 rearrangement without the typical fusion variants by RT-PCR, or any MYH9 rearrangement by FISH. We sought to further characterize such tumors using molecular diagnostic assays. A novel RT-PCR assay was designed to detect the two known MYH9-USP6 fusion types in formalin-fixed paraffin-embedded and frozen tissue, and a break-apart FISH assay was designed to detect USP6 rearrangement. Twenty-six cases of nodular fasciitis diagnosed between 2002 and 2013 were retrieved from the pathology files of our institutions and were confirmed to be positive by FISH and/or RT-PCR. Seven samples showed USP6 rearrangement by FISH but were negative for MYH9-USP6 fusion by RT-PCR; these cases were subjected to a next-generation sequencing assay utilizing anchored multiplex PCR technology. This assay targets a single partner gene associated with fusions in bone and soft tissue tumors for agnostic detection of gene fusion partners. Novel fusion partners were identified in all seven cases and confirmed by RT-PCR. Structurally, all fusions consisted of the juxtaposition of the entire coding region of USP6 with the promoter of the partner gene, driving increased USP6 expression. This study confirms the neoplastic nature of nodular fasciitis, defines additional pathogenic fusion partners, and adds to the growing body of literature on USP6-associated neoplasia. Given the diagnostic challenges of these tumors, molecular assays can be useful ancillary tools; however, the prevalence of promoter swapping must be recognized when interpreting results.

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Section: Discussionmentioning

confidence: 99%

USP6 activation in nodular fasciitis by promoter-swapping gene fusions

et al. 2017

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“…The SPARC protein family consists of SPARC (Osteonectin, BM‐40), SPARC‐like 1, SOMC, testican, and follistatin‐like protein 1 . SPARC has a complex role in many cancers.…”

Section: Discussionmentioning

confidence: 99%

“…The SPARC protein family consists of SPARC (Osteonectin, BM-40), SPARC-like 1, SOMC, testican, and follistatin-like protein 1. 32 SPARC has a complex role in many cancers. On the one hand, SPARC acts as a tumor suppressor to inhibit migration and invasion of breast cancer cells and inhibits tumor growth and angiogenesis in neuroblastoma.…”

Section: Discussionmentioning

confidence: 99%

Secreted protein acidic and rich in cysteine promotes epithelial–mesenchymal transition of hepatocellular carcinoma cells and acquisition of cancerstem cell phenotypes

Jiang

Liu

Wang

2019

J of Gastro and Hepatol

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Background and Aim Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that plays a significant role in tumor development. SPARC has been indicated that promotes tumorigenesis, metastasis, and poor prognosis in prostate cancer and lung cancer. Therefore, we sought to investigate the molecular mechanisms of SPARC in regulating hepatocellular carcinoma (HCC). Methods We used spheroids cultured in serum‐free culture medium to obtain liver cancer stem cells. Flow cytometric analysis was performed to investigate percentage of CD133+ cells in liver cancer cells. Real‐time polymerase chain reaction and western blot were used to assess gene expression in cell lines. Transwell and wound healing assays were performed to indicate cell migration of HCC. Results Secreted protein acidic and rich in cysteine was upregulated in spheres formation in HCC cells. Overexpression of SPARC enhanced the ability to form tumor spheres and increased CD133 and Oct4 expressions. Besides, SPARC promoted the migration and epithelial–mesenchymal transition in HCC cells. Importantly, SPARC overexpression stimulated the formation of subcutaneous tumors in nude mice. Conclusions Our findings suggest that SPARC overexpression promotes tumor growth, inducing epithelial–mesenchymal transition and acquisition of a stem cell phenotype. What is more, research elucidating the biological mechanisms of SPARC may be beneficial to liver cancer treatment.

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“…Many prior studies indicated a strong association between elevated SPARC expression and tissue fibrosis. 18,19 Seet et al 20 found that SPARC deficiency resulted in improved surgical survival in a novel mouse model of glaucoma filtration surgery. They also revealed that SPARC modulated the wound fibrosis by delaying cell migration, reducing collagen contractility, and lowering expressions of profibrotic genes.…”

Section: Discussionmentioning

confidence: 99%