Sparc

Abstract

In an attempt to identify genetic alterations occurring early in astrocytoma progression, we performed subtractive hybridization between astrocytoma and glioblastoma cDNA libraries. We identified secreted protein acidic and rich in cysteine (SPARC), a protein implicated in cell-matrix interactions, as a gene overexpressed early in progression. Northern blot and immunohistochemical analyses indicated that transcript and protein were both elevated in all tumor specimens (grades II-IV) examined when compared with levels in normal brain. The level of SPARC expression was found to be tumor-dependent rather than grade-related. Immunohistochemically, SPARC protein was found to be overexpressed in 1) cells in the less cellularly dense regions within the tumor mass, 2) histomorphologically neoplastic-looking cells in adjacent normal brain at the tumor/brain interface, 3) neovessel endothelial cells in both the tumor and adjacent normal brain, and 4) reactive astrocytes in normal brain adjacent to tumor. Using a combination of DNA in situ hybridization and protein immunohistochemical analyses of the human/rat xenograft, SPARC expression was observed in the human glioma cells within the tumor mass, and in cells that invaded along vascular basement membranes and individually into the rat brain parenchyma, suggesting it may be an invasion-related gene. While it remains to be determined whether SPARC functionally contributes to tumor cell invasion, these data suggest that the early onset of increased SPARC expression, though complex, may serve as a signal indicative of neoplastic astrocytic transformation and reactive response to tumor-induced stress.

A Novel Interaction between Procaspase 8 and SPARC Enhances Apoptosis and Potentiates Chemotherapy Sensitivity in Colorectal Cancers

“…Its role in tumorigenesis has been examined in a variety of cancers (9,(35)(36)(37)(38) including hematological malignancies (12), with diverging actions that may be attributed to tissue-related differences. Previously, we demonstrated that SPARC gene and protein expression changes the sensitivity of therapy-refractory MIP101 CRC cells to chemotherapy in vitro and in vivo by enhancing apoptosis and tumor regression (9).…”

Secreted Protein Acidic, Rich in Cysteine (SPARC), Mediates Cellular Survival of Gliomas through AKT Activation

“…SPARC induces an intermediate stage of cellular adhesion with ablation of focal adhesions, regulates matrix deposition, and induces growth inhibition in endothelial cells (5,6,10). In addition to its normal physiological role, SPARC has been linked to cancer progression as many cancer types express increased SPARC levels upon invasion or metastasis (5,6,11,12). Malignant gliomas rarely metastasize but are highly invasive leading to a failure of curative surgery (13).…”

“…Malignant gliomas rarely metastasize but are highly invasive leading to a failure of curative surgery (13). Gliomas express SPARC at sites of invasion and neoangiogenic blood vessels at the braintumor interface (11,14). We and others have shown that malignant glioma cell lines engineered to overexpress SPARC adopt an invasive phenotype both in vitro and in vivo associated with an increased expression of specific matrix metalloproteinases (15)(16)(17).…”

Preclinical Mouse Models of Neurofibromatosis

“…28 We, therefore, compared the effects of 13cRA on CFU-GM growth from Mx1-Cre, Nf1 flox/flox and control bone marrows. As shown in Figure 3, Mx1-Cre, Nf1 flox/flox marrows contained elevated numbers of CFU-GM, which were larger than wild-type colonies.…”

“…The final step in Ras processing involves methylation of the prenylcysteine by isoprenylcysteine carboxyl methyltransferase (Icmt). Genetic experiments performed by Dr. Shannon's lab showed no detectable effects of ablating Rce1 on normal hematopoiesis (28).…”