SPARC in cancer biology: Its role in cancer progression and potential for therapy

Tai, Isabella T.; Tang, Michelle

doi:10.1016/j.drup.2008.08.005

Cited by 203 publications

(198 citation statements)

References 125 publications

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“…The discrepancy in the pathological outcome evident in these studies might be due to the differences in genetic background of the mice used in the study. Similarly, controversy over the role of SPARC was also evident in carcinoma of breast and skin, where both oncogenic and tumor-suppressive roles were observed in multiple in vitro, in vivo, and clinical studies (50). On the other hand, the tumorand metastasis-suppressive role of SPARC has been well documented for gastrointestinal, ovarian, pancreatic, and colon cancers, whereas the oncogenic role was verified in glioma (38,(51)(52)(53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, a previous study has shown that tumor-stroma interaction in the bone elevates SPARC expression in the bone microenvironment, followed by proteolytic cleavage by the stromal collagenase cathepsin K, although the specific role of SPARC fragments in bone metastasis was not examined (58). It is noteworthy that opposing biological roles of SPARC fragments have been identified previously (50). Therefore, the differences in the protease profile of the microenvironment may potentially dictate the functional fate of the cleaved fragments, which warrants further studies to identify the functions of individual peptides during the pathological stages of bone metastasis.…”

Section: Recurrence Dormancymentioning

confidence: 99%

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Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone

Sharma

Xing

Yin

et al. 2016

Journal of Biological Chemistry

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Prostate cancer is known to frequently recur in bone; however, how dormant cells switch its phenotype leading to recurrent tumor remains poorly understood. We have isolated two syngeneic cell lines (indolent and aggressive) through in vivo selection by implanting PC3mm stem-like cells into tibial bones. We found that indolent cells retained the dormant phenotype, whereas aggressive cells grew rapidly in bone in vivo, and the growth rates of both cells in culture were similar, suggesting a role of the tumor microenvironment in the regulation of dormancy and recurrence. Indolent cells were found to secrete a high level of secreted protein acidic and rich in cysteine (SPARC), which significantly stimulated the expression of BMP7 in bone marrow stromal cells. The secreted BMP7 then kept cancer cells in a dormant state by inducing senescence, reducing "stemness," and activating dormancy-associated p38 MAPK signaling and p21 expression in cancer cells. Importantly, we found that SPARC was epigenetically silenced in aggressive cells by promoter methylation, but 5-azacytidine treatment reactivated the expression. Furthermore, high SPARC promoter methylation negatively correlated with disease-free survival of prostate cancer patients. We also found that the COX2 inhibitor NS398 down-regulated DNMTs and increased expression of SPARC, which led to tumor growth suppression in bone in vivo. These findings suggest that SPARC plays a key role in maintaining the dormancy of prostate cancer cells in the bone microenvironment.

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Section: Discussionmentioning

confidence: 99%

Section: Recurrence Dormancymentioning

confidence: 99%

Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone

Sharma

Xing

Yin

et al. 2016

Journal of Biological Chemistry

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“…Its function in cancer is discussed in a very controversial manner (Clark and Sage, 2008;Podhajcer et al, 2008;Tai and Tang, 2008). In certain types of cancers, such as melanomas and gliomas, SPARC is associated with a highly aggressive tumour phenotype.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expression

et al. 2009

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BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is a multi-faceted protein-modulating cell -cell and cell -matrix interactions. In cancer, SPARC can be not only associated with a highly aggressive phenotype, but also acts as a tumour suppressor. The aim of this study was to characterise the function of SPARC and its modulation by fibroblast growth factor receptor (FGFR) 1 isoforms in pancreatic ductal adenocarcinoma (PDAC). METHODS AND RESULTS: Exogenous SPARC inhibited growth, movement, and migration. ShRNA inhibition of endogenous SPARC in ASPC-1 and PANC-1 cells resulted in increased anchorage-dependent and -independent growth, transwell migration, and xenograft growth as well as increased mitogenic efficacy of fibroblast growth factor (FGF) 1 and FGF2. Endogenous SPARC expression in PANC-1 cells was increased in FGFR1-IIIb over-expressing cells, but decreased in FGFR1-IIIc over-expressing cells. The up-regulation of endogenous SPARC was abrogated by the p38-mitogen-activated protein kinase inhibitor SB203580. SPARC was detectable in conditioned medium of pancreatic stellate cells (PSCs), but not PDAC cells. Conditioned medium of PDAC cells reduced endogenous SPARC expression of PSCs. CONCLUSION: Endogenous SPARC inhibits the malignant phenotype of PDAC cells and may, therefore, act as a tumour suppressor in PDAC. Endogenous SPARC expression can be modulated by FGFR1-III isoform expression. In addition, PDAC cells may inhibit endogenous SPARC expression in surrounding PSCs by paracrine actions.

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“…[1][2][3][4] Although it is expressed by different types of cancers, its expression pattern and prognostic implications vary. 5,6 Elevated SPARC expression is associated with disease progression and poor prognosis in melanoma, breast cancer, glioma, bladder cancer and non-small cell lung cancer. [7][8][9][10][11][12] In colorectal cancer (CRC), the role of SPARC is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Lymphovascular invasion of colorectal cancer is correlated to SPARC expression in the tumor stromal microenvironment

Yoshimura

Nagahara²,

Kuo³

et al. 2011

Epigenetics

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SPARC in cancer biology: Its role in cancer progression and potential for therapy

Cited by 203 publications

References 125 publications

Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone

Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone

Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expression

Lymphovascular invasion of colorectal cancer is correlated to SPARC expression in the tumor stromal microenvironment

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