Growth Factors as Active Participants in Carcinogenesis: A Perspective

Halper, Jaroslava

doi:10.1177/0300985809352981

Cited by 41 publications

(31 citation statements)

References 267 publications

(338 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…GP88 (progranulin) has been shown to play a role in the pathogenesis of several cancers and has been demonstrated to be an autocrine growth and survival factor in cancer cells and also to stimulate angiogenesis, migration and invasion (7, 10). Increased GP88 expression is associated with increased tumorigenicity and drug resistance.…”

Section: Discussionmentioning

confidence: 99%

GP88 (progranulin): a novel tissue and circulating biomarker for non–small cell lung carcinoma

et al. 2014

View full text Add to dashboard Cite

GP88 (progranulin) is a growth and survival factor implicated in tumorigenesis and drug resistance. Previous studies showed that GP88 was expressed in breast cancer tissue in inverse correlation with survival. This study evaluates GP88 tissue expression in localized/locally advanced lung cancer and GP88 serum levels in advanced disease. GP88 expression was determined by immunohistochemistry in tumor tissue from non-small cell carcinoma (NSCLC) patients, 85 with localized (Stage I-II) and 40 with locally advanced disease (Stage IIIa) and correlated with clinical outcome. Serum GP88 levels from Stage IIIb/IV patients, quantified by Enzyme Immunoassay (EIA) were compared to GP88 levels from patients with Chronic Obstructive Pulmonary Disease (COPD) and healthy individuals. GP88 was expressed in >80% adenocarcinoma and squamous cell carcinoma in contrast to normal lung or small cell lung cancer. There was a statistically significant inverse association of GP88 expression (GP88 Immunohistochemistry score 3+ vs. <3+) with survival for patients with localized resected NSCLC with Hazard Ratio (HR)=2.28 (p=0.0076) for DFS and HR=2.17 (p=0.014) for OS. A statistically significant decrease in progression-free survival (HR=2.9, p=0.022) for GP88 scores of 3+ vs. <3+ was observed for Stage IIIa after chemoradiotherapy. In addition, serum GP88 was significantly elevated in Stage IIIb/IV NSCLC compared to control subjects (49.9ng/ml vs. 28.4ng/ml, p<0.0001). This is the first study demonstrating GP88 tissue and serum expression as a prognostic biomarker in localized and advanced disease. Future research will determine utility of monitoring GP88 and the potential of GP88 expression as a predictive marker for anti-GP88 therapeutics.

show abstract

Section: Discussionmentioning

confidence: 99%

GP88 (progranulin): a novel tissue and circulating biomarker for non–small cell lung carcinoma

et al. 2014

View full text Add to dashboard Cite

show abstract

“…VEGF, b-FGF and TGF-β1 are growth factors with multiple biological functions that play important roles in enhancing tumor cell proliferation, angiogenesis and tumor development [17–19]. To gain insight into the mechanism for enhanced proliferation, tumorigenicity and adhesion by LeY antigen, we examined the expression of TGF-β1, VEGF and b-FGF in both nude mouse xenograft tumors and cells cultured in vitro by immunohistochemical staining and Western blot analysis, respectively.…”

Section: Resultsmentioning

confidence: 99%

Lewis Y Promotes Growth and Adhesion of Ovarian Carcinoma-Derived RMG-I Cells by Upregulating Growth Factors

Lin

Hao

et al. 2010

IJMS

View full text Add to dashboard Cite

Lewis y (LeY) antigen is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Overexpression of LeY is frequently observed in epithelial-derived cancers and has been correlated to the pathological staging and prognosis. However, the effects of LeY on ovarian cancer are not yet clear. Previously, we transfected the ovarian cancer cell line RMG-I with the α1,2-fucosyltransferase gene to obtain stable transfectants, RMG-I-H, that highly express LeY. In the present study, we examined the proliferation, tumorigenesis, adhesion and invasion of the cell lines with treatment of LeY monoclonal antibody (mAb). Additionally, we examined the expression of TGF-β1, VEGF and b-FGF in xenograft tumors. The results showed that the proliferation and adhesion in vitro were significantly inhibited by treatment of RMG-I-H cells with LeY mAb. When subcutaneously inoculated in nude mice, RMG-I-H cells produced large tumors, while mock-transfected cells RMG-I-C and the parental cells RMG-I produced small tumors. Moreover, the tumor formation by RMG-I-H cells was inhibited by preincubating the cells with LeY mAb. Notably, the expression of TGF-β1, VEGF and b-FGF all increased in RMG-I-H cells. In conclusion, LeY plays an important role in promoting cell proliferation, tumorigenecity and adhesion, and these effects may be related to increased levels of growth factors. The LeY antibody shows potential application in the treatment of LeY-positive tumors.

show abstract

“…GP88 overexpression of several growth factors or growth factor receptors has been found to be associated with tamoxifen resistance, especially in MCF-7 cells [5]. Her-2 receptor overexpression promotes tamoxifen resistance in MCF-7 [28]. However, in this case, the resistance corresponded to a decreased ability of tamoxifen to inhibit tumor growth in vivo rather than a complete loss of tamoxifen response.…”

Section: Discussionmentioning

confidence: 99%

“…This protein has been found to have pleiotropic functions in normal and diseased human tissues. In particular, GP88 has been found to be overexpressed in many cancers whereas it is not expressed in the normal tissue counterparts [26]- [28]. GP88 stimulates proliferation, survival and metastasis in several cancer cell types via activation of multiple pathways that include MAP kinase and P-I-3 kinase pathways, FAK kinase [27].…”

Section: Introductionmentioning

confidence: 99%

GP88 (Progranulin) Confers Fulvestrant (Faslodex, ICI 182,780) Resistance to Human Breast Cancer Cells

Tangkeangsirisin¹,

Serrero²

2014

ABCR

View full text Add to dashboard Cite

The 88 kDa glycoprotein known as GP88, Progranulin or PC cell derived growth factor is an autocrine growth factor with a unique cysteine rich motif that is over expressed in breast cancer whereas it is negative in normal mammary epithelial cells. It has been shown to play a major role in estrogen independence, tamoxifen resistance and tumorigenesis of breast cancer cells. In the present study, we investigated the effect of GP88 overexpression on the response of the human breast cancer MCF-7 cells to the pure estrogen receptor antagonist fulvestrant (ICI 182,780). While fulvestrant effectively inhibited cell proliferation of empty vector transfected cells, it had no inhibitory effect on the proliferation of GP88 overexpressing breast cancer cells. Mouse xenograft experiments in athymic ovariectomized nude mice showed that GP88 over expressing cells were fulvestrant resistant in vivo in contrast to low GP88 expressing cells. We show that the ability of fulvestrant to induce apoptosis determined by measuring cleavage of poly (ADP-ribose) polymerase was inhibited by GP88. Anti-apoptotic activity of GP88 was associated with sustained expression of bcl-2 and bcl-xL after fulvestrant treatment. In contrast, fulvestrant was still able to inhibit the ability of estrogen to stimulate ERE-luciferase reporter gene activity as well as vEGF expression in GP88 over expressing MCF-7 cells similarly to control MCF-7 cells. Collectively, our data suggest that GP88 prevents apoptosis induced by faslodex and contributes to antiestrogen resistance in human breast cancer.

show abstract

Growth Factors as Active Participants in Carcinogenesis: A Perspective

Cited by 41 publications

References 267 publications

GP88 (progranulin): a novel tissue and circulating biomarker for non–small cell lung carcinoma

GP88 (progranulin): a novel tissue and circulating biomarker for non–small cell lung carcinoma

Lewis Y Promotes Growth and Adhesion of Ovarian Carcinoma-Derived RMG-I Cells by Upregulating Growth Factors

GP88 (Progranulin) Confers Fulvestrant (Faslodex, ICI 182,780) Resistance to Human Breast Cancer Cells

Contact Info

Product

Resources

About