Fibronectin acts as a molecular switch to determine SPARC function in pancreatic cancer

Munasinghe, Amanda; Malik, Khalisha; Mohamedi, Fatemia; Moaraf, Stan; Kocher, Hemant M.; Jones, Lucy; Hill, Natasha J.

doi:10.1016/j.canlet.2020.02.031

Cited by 19 publications

(16 citation statements)

References 49 publications

(62 reference statements)

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“…SPARC, which is also called osteonectin, is a component of the bone matrix that modulates cellular interactions with the extracellular matrix, exerting an adhesive, promigratory effect on cells. [72][73][74] Studies confirmed that high expression of SPARC in most of the tumors with a tendency for bone metastasis. 75,76 In PCa, Sarmishtha De et al treated tumor cells with different antagonists and conclude that tumor cells on the bone surface linked with SPARC exhibit αvβ3 expression.…”

Section: Vegf Promotes Pca Bone Metastasis By Controlling αVβ3 and Spmentioning

confidence: 72%

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

Tang¹,

Xu²,

Zhang³

et al. 2020

OTT

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In prostate cancer, distant organ metastasis is the leading cause of patient death. Although the mechanism of malignant tumor metastasis is unclear, studies have confirmed that integrin αVβ3 plays an important role in this process. In prostate cancer, αVβ3 mediates adhesion, invasion, immune escape and neovascularization through interactions with different ligands. Among these ligands and in addition to proteins that are directly related to tumor invasion, other proteins that contain the RGD structure could also bind to αVβ3 and cause a number of biological effects. In this article, we summarized the ligand and downstream proteins related to αVβ3-mediated prostate cancer metastasis as well as some diagnostic and therapeutic measures targeting αVβ3.

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Section: Vegf Promotes Pca Bone Metastasis By Controlling αVβ3 and Spmentioning

confidence: 72%

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

Tang¹,

Xu²,

Zhang³

et al. 2020

OTT

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“…switched the function of SPARC from promoting cancer cell proliferation to growth inhibition and induction of apoptosis (Munasinghe et al, 2020). Although BGLAP was known crucial during bone remodeling, the function remained largely unknown and it arose great interest recently as a bone-derived hormone in regulation of energy metabolism (Li et al, 2016;Zoch et al, 2016;Mera et al, 2018;Moser and van der Eerden, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…It’s worth noting that the influence of SPARC on tumor progression depended on the initiating cell type, tumor stage and context of the microenvironment ( Tai and Tang, 2008 ; Arnold and Brekken, 2009 ; Rossi et al, 2016 ). Notably, Munasinghe et al reported that depletion of fibronectin switched the function of SPARC from promoting cancer cell proliferation to growth inhibition and induction of apoptosis ( Munasinghe et al, 2020 ). Although BGLAP was known crucial during bone remodeling, the function remained largely unknown and it arose great interest recently as a bone-derived hormone in regulation of energy metabolism ( Li et al, 2016 ; Zoch et al, 2016 ; Mera et al, 2018 ; Moser and van der Eerden, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analyses Reveal Prognostic Value of Osteomimicry Across 20 Solid Cancer Types

Yang

Pan

Shen

2020

Front. Mol. Biosci.

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Background: Osteomimicry of cancer cells had been widely reported in prostate cancer and breast cancer. However, the prognostic value of osteomimicry in various cancer types remained unclear. We hypothesized that osteomimicry would result in remodeling of the tumor microenvironment and was eligible to predict patient prognosis. Methods: A comprehensive transcriptomic analysis of the osteomimicry, which was characterized by mRNA expression of SPARC, SPP1, and BGLAP, across 20 solid tumors (7564 patients) using RNA-seq data from The Cancer Genome Atlas (TCGA) was conducted. Samples of each cancer type were classified into subgroups (high vs. low) based on median value of osteomimetic markers, the associations of these markers with clinical outcomes, immune cell infiltration and immune checkpoints expression were explored. Results: Each osteomimetic marker harbored prognostic value in the pan-cancer analyses [SPARC: hazard ratio (HR) = 1.10, p = 0.028; SPP1: HR = 1.25, p < 0.001; BGLAP: HR = 1.13, p = 0.005]. Patients with high expression of all the three genes also had significantly unfavorable survival (HR = 1.61, p < 0.0001) compared with those of low expression. Correlation analyses demonstrated that osteomimicry was closely related to tumor purity, dendritic cells (DC) infiltration and expression of immune checkpoints. Conclusion: Osteomimicry had prognostic value in various cancer types and the underlying mechanism might correlate to the trapping and dysfunction of DCs in the tumor microenvironment, revealing the potential of osteomimicry as a target of immunotherapy.

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“…The anti-tumor activity of EMAP II is mediated through targeted interference with stroma fibronectin-integrin dependent pancreatic cancer cell proliferation [96]. New findings indicate that the depletion of fibronectin switches the activity of secreted protein acidic cysteine-rich (SPARC) from promoting cancer cell proliferation to growth inhibition and induction of apoptosis [97].…”

Section: Modulation Of Cafs To Treat Pancreatic Cancermentioning

confidence: 99%

Pancreatic Cancer Associated Fibroblasts (CAF): Under-Explored Target for Pancreatic Cancer Treatment

Norton

Foster

Chinta

et al. 2020

Cancers

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Pancreatic cancer is the 4th leading cause of cancer deaths in the United States. The pancreatic cancer phenotype is primarily a consequence of oncogenes disturbing the resident pancreas parenchymal cell repair program. Many solid tumor types including pancreatic cancer have severe tumor fibrosis called desmoplasia. Desmoplastic stroma is coopted by the tumor as a support structure and CAFs aid in tumor growth, invasion, and metastases. This stroma is caused by cancer associated fibroblasts (CAFs), which lay down extensive connective tissue in and around the tumor cells. CAFs represent a heterogeneous population of cells that produce various paracrine molecules such as transforming growth factor-beta (TGF-beta) and platelet derived growth factors (PDGFs) that aid tumor growth, local invasion, and development of metastases. The hard, fibrotic shell of desmoplasia serves as a barrier to the infiltration of both chemo- and immunotherapy drugs and host immune cells to the tumor. Although there have been recent improvements in chemotherapy and surgical techniques for management of pancreatic cancer, the majority of patients will die from this disease. Therefore, new treatment strategies are clearly needed. CAFs represent an under-explored potential therapeutic target. This paper discusses what we know about the role of CAFs in pancreatic cancer cell growth, invasion, and metastases. Additionally, we present different strategies that are being and could be explored as anti-CAF treatments for pancreatic cancer.

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Fibronectin acts as a molecular switch to determine SPARC function in pancreatic cancer

Cited by 19 publications

References 49 publications

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

Pan-Cancer Analyses Reveal Prognostic Value of Osteomimicry Across 20 Solid Cancer Types

Pancreatic Cancer Associated Fibroblasts (CAF): Under-Explored Target for Pancreatic Cancer Treatment

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