Vascular endothelial growth factor receptor‐1 promotes migration and invasion in pancreatic carcinoma cell lines

Wey, Jane; Fan, Bingbing; Gray, Michael J.; Bauer, Todd W.; McCarty, Marya F.; Somcio, A B Ray; Liu, Wenbiao; Evans, Douglas B.; Wu, Yan; Hicklin, Daniel J.; Ellis, Lee M.

doi:10.1002/cncr.21145

Cited by 179 publications

(144 citation statements)

References 95 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…However, recent reports demonstrate that flt-1 is present and functional on different human cancer cells and that activation of flt-1 by VEGF can activate processes involved in tumor progression and metastasis (12,33,35). Thus, we suggest that the FLT1-SNP allele may be a significant risk factor in the development of angiogenesis-driven diseases.…”

Section: Discussionmentioning

confidence: 70%

A SNP in the flt-1 promoter integrates the VEGF system into the p53 transcriptional network

Menéndez

Krysiak

Inga

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The VEGF system is essential for angiogenesis. VEGF overexpression frequently correlates with increased microvascularity and metastasis and decreased spontaneous apoptosis. Although a precise mechanism has not been established, studies suggest that VEGF expression is negatively regulated by p53, a master regulator and tumor suppressor. There are no reports of additional components of the VEGF signal transduction pathway being part of the p53 transcriptional network. A target of VEGF, the VEGF receptor 1͞flt-1, can regulate growth and migration of endothelial cells and modulate angiogenesis. VEGF appears to be up-regulated in various cancers in which flt-1 may have a role in tumor progression and metastasis. We identified a C-to-T SNP upstream of the transcriptional start site in Ϸ6% of the people examined. The SNP is located within a putative p53 response element. Only the promoter with the T SNP (FLT1-T) was responsive to p53 when examined with reporter assays or by endogenous gene expression analysis in cell lines with different SNP status. In response to doxorubicin-induced DNA damage, there was clear allele discrimination based on p53 binding at the FLT1-T but not FLT1-C promoters as well as p53-dependent induction of flt-1 mRNA, which required the presence of FLT1-T. Our results establish that p53 can differentially stimulate transcription at a polymorphic variant of the flt-1 promoter and directly places the VEGF system in the p53 stress-response network via flt-1 in a significant fraction of the human population. We suggest that the p53-VEGF-flt-1 interaction is relevant to risks in angiogenesis-associated diseases, including cancer.single-nucleotide polymorphism ͉ genotoxic stress ͉ VEGF receptor 1 ͉ cancer cells

show abstract

Section: Discussionmentioning

confidence: 70%

A SNP in the flt-1 promoter integrates the VEGF system into the p53 transcriptional network

Menéndez

Krysiak

Inga

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…VEGF and its 3 principal receptors (VEGFR-1,VEGFR-2 and VEGFR-3) were expressed to varying degrees in tumors of the pancreas. Overexpression of VEGF in tumors may activate tumor cells bearing VEGFR-1 via an autocrine pathway [92]. VEGFR-1 plays a role in tumor progression in pancreatic cancer through the induction of epithelial to mesenchymal transition [93].…”

Section: Pancreatic Cancermentioning

confidence: 99%

VEGF expression in pancreatic cancer and other malignancies: a review of the literature

Costache

Ioana

Iordache

et al. 2015

Romanian Journal of Internal Medicine

View full text Add to dashboard Cite

Angiogenesis is a crucial event for tumor growth and it is regulated predominantly by several different growth factors. Vascular endothelial growth factor protein family (VEGF) and its receptors are probably the most important tissue factors responsible for angioblast differentiation and tube formation. VEGF protein family currently comprises several members: VEGF (or VEGF-A), VEGF-B, VEGF-C and VEGF-D, VEGF-F, placental growth factor (PlGF), and their receptors VEGFR-1, VEGFR-2 and VEGFR-3. VEGF is a key angiogenic growth factor and its level of expression is a critical marker for detection of the angiogenic diseases. The potent role of VEGF in tumor angiogenesis has been widely described in the past decade, being expressed in most types of nondigestive and digestive cancers. VEGF family members play an important role in the development of pancreatic cancer (especially VEGF-A, VEGF-C, VEGF-D, VEGFR-1 and VEGFR-2). VEGF-A is the most specific and prominent angiogenic factor among all family members and VEGFR-2 is the most important receptor in evaluating the angiogenesis in pancreatic cancer. Thus, VEGF overexpression may be considered as a diagnostic marker and as a poor prognostic factor of the disease.

show abstract

“…The potential pleiotropic effects of anti-VEGF therapy is in part due to the fact that VEGF receptors are expressed not only on endothelial cells in tumors, but also on subsets of hematopoietic cells, stromal cells, in addition to malignant cells in certain human cancers (e.g. breast, brain, colorectal and pancreatic [11,[38][39][40]). The existing clinical data on the mechanisms of action of anti-VEGF therapy that have been suggested by preclinical studies [9,11,12] are discussed below.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects

Duda

Batchelor

Willett

et al. 2007

Trends in Molecular Medicine

123

View full text Add to dashboard Cite

Despite setbacks, the clinical development of antiangiogenic agents has accelerated remarkably over the past 3-4 years. Consequently, there are currently three direct inhibitors of the VEGF pathway approved for use in cancer therapy. Other agents that block the VEGF pathway are in advanced stages of clinical development and have shown promising results. With these exciting developments come crucial questions regarding the use of these new molecular-targeted agents, alone or in combination with standard cytotoxic or targeted agents. Importantly, the mechanisms of action of anti-VEGF therapy remain unknown. Here, we discuss several potential mechanisms of action such as tumor vascular normalization, bone marrow-derived cell recruitment blockade and cytostatic effects of anti-VEGF therapy. We review the current progress, the major stumbling blocks and the future directions for anti-cancer therapy using anti-VEGF agents, emphasizing clarification of the underlying molecular mechanisms of action and biomarker identification and validation.

show abstract

Vascular endothelial growth factor receptor‐1 promotes migration and invasion in pancreatic carcinoma cell lines

Cited by 179 publications

References 95 publications

A SNP in the flt-1 promoter integrates the VEGF system into the p53 transcriptional network

A SNP in the flt-1 promoter integrates the VEGF system into the p53 transcriptional network

VEGF expression in pancreatic cancer and other malignancies: a review of the literature

VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects

Contact Info

Product

Resources

About