Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes

Watkins, Gareth; Douglas-Jones, Anthony; Bryce, Richard; Mansel, Robert Edward; Jiang, Wen Guo

doi:10.1016/j.plefa.2004.12.003

Cited by 131 publications

(106 citation statements)

References 17 publications

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“…SPARC is also thought to play an important role in tissue remodelling, angiogenesis, embryonic development and tumorigenesis. The levels of SPARC in breast tumor tissues were significantly higher compared to normal background breast tissue, which has been previously reported in advanced breast cancers and node-positive tumors [34]. Likewise, our analysis revealed that secretion of SPARC was elevated in the relatively aggressive MCF10 DCIS.com and MCF10CA cl.…”

Section: Validation Of the Lc-ms Datasupporting

confidence: 85%

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

et al. 2007

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Proteins secreted (the secretome) from cancer cells are potentially useful as biomarkers of the disease. Using LC-MS/MS, the secreted proteomes from a series of isogenic breast cancer cell lines varying in aggressiveness were analyzed by mass spectrometry: non-tumorigenic MCF10A, premalignant/ tumorigenic MCF10AT, tumorigenic/locally invasive MCF10 DCIS.com and tumorigenic/ metastatic MCF 10CA cl. D. Proteomes were obtained from conditioned serum-free media, partially fractionated using a small reverse phase C2 column and digested with trypsin for analysis by LC-MS/MS, using a method previously shown to give highly enriched secreted proteomes (Mbeunkui, et. al., J. Prot. Res. 5, 899-906 2006). The search files produced from 5 analyses (3 separate preparations) were combined for database searching (Mascot) which produced a list of over 250 proteins from each cell line. The aim was to discover highly secreted proteins which changed significantly in abundance corresponding with aggressiveness. The most apparent changes were observed for alpha-1-antichymotrypsin and galectin-3-binding protein which were highly secreted proteins from MCF10 DCIS.com and MCF10CA cl. D, yet undetected in the MCF10A and MCF10AT cell lines. Other proteins showing increasing abundance in the more aggressive cell lines included alpha-1-antitrypsin, cathepsin D and lysyl oxidase. The S100 proteins, often associated with metastasis, showed variable changes in abundance. While the cytosolic proteins were low (e.g. actin and tubulin), there was significant secretion of proteins often associated with the cytoplasm. These proteins were all predicted as products of non-classical secretion (SecretomeIP, Center for Biological Sequence Analysis). The LC-MS/MS results were verified for five selected proteins by western blot analysis, and the relevance of other significant proteins is discussed. Comparisons with two other aggressive breast cancer cell lines are included and the protein with consistent association with aggressiveness in all lines, and in unrelated cancer cells, was the galectin-3-binding protein which has been associated with breast, prostate and colon cancer earlier, supporting the approach and findings. This analysis of an isogenic series of cell lines suggests the potential usefulness of the secretome for identifying prospective markers for the early detection and aggressiveness/progression of cancer.

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Section: Validation Of the Lc-ms Datasupporting

confidence: 85%

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

et al. 2007

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“…However, as SPARC has the potential to function both as a tumor promoter and tumor suppressor, decreasing SPARC expression may not be beneficial for all tumor types or stages. For example, SPARC induces apoptosis in ovarian cancer cells (Yiu et al, 2001) and inhibits proliferation and metastasis of breast cancer cells (Koblinski et al, 2005), but breast tumor expression of SPARC is linked to increased patient metastases and poor patient survival (Jones et al, 2004;Watkins et al, 2005). When we overexpressed SPARC in HeLa cells or a genetically engineered human breast cancer model (HMEC), SPARC-expressing cells suffered a dramatic inhibition of tumor formation when implanted into immunocompromised rodents (data not shown).…”

Section: Discussionmentioning

confidence: 98%

Targeting SPARC expression decreases glioma cellular survival and invasion associated with reduced activities of FAK and ILK kinases

et al. 2007

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Secreted protein acidic and rich in cysteine (SPARC) is an extracellular glycoprotein expressed in several solid cancers, including malignant gliomas, upon adoption of metastatic or invasive behaviors. SPARC expression in glioma cells promotes invasion and survival under stress, the latter process dependent on SPARC activation of AKT. Here we demonstrate that downregulation of SPARC expression with short interfering RNA (siRNA) in glioma cells decreased tumor cell survival and invasion. SPARC siRNA reduced the activating phosphorylation of AKT and two cytoplasmic kinases, focal adhesion kinase (FAK) and integrin-linked kinase (ILK). We determined the contributions of FAK and ILK to SPARC effects using SPARC protein and cell lines engineered to overexpress SPARC. SPARC activated FAK and ILK in glioma cells previously characterized as responsive to SPARC. Downregulation of either FAK or ILK expression inhibited SPARC-mediated AKT phosphorylation, and targeting both FAK and ILK attenuated AKT activation more potently than targeting either FAK or ILK alone. Decreased SPARC-mediated AKT activation correlated with a reduction in SPARC-dependent invasion and survival upon the downregulation of FAK and/or ILK expression. These data further demonstrate the role of SPARC in glioma tumor progression through the activation of intracellular kinases that may provide novel therapeutic targets for advanced cancers.

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“…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. 13,14 SPARC is expressed not only by cancer cells but also by stromal cells surrounding the tumor.…”

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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Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes

Cited by 131 publications

References 17 publications

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

Targeting SPARC expression decreases glioma cellular survival and invasion associated with reduced activities of FAK and ILK kinases

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

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