Inhibiting tumor growth of colorectal cancer by blocking the expression of vascular endothelial growth factor receptor 3 using interference vector-based RNA interference

Lui, Zhicheng; Ma, Qingjie; Wang, Xianghui; Zhang, Youcheng

doi:10.3892/ijmm_00000313

Cited by 7 publications

(1 citation statement)

References 19 publications

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“…Moreover, VEGFR3 has been shown to be important in other tumor types. Knockdown of VEGFR3 expression with siRNA in colorectal or breast cancer cell lines has been shown to reduce tumor cell proliferation in vitro and to significantly inhibit tumor growth in vivo [35, 36], indicating that VEGFR3 inhibition is sufficient to inhibit tumor growth. Collectively, our results highlight that VEGFR3 is a critical receptor for myxoid liposarcoma cell survival and suggest that myxoid liposarcoma cells may display oncogenic addiction to VEGFR3 signaling.…”

Section: Discussionmentioning

confidence: 99%

Axitinib Has Antiangiogenic and Antitumorigenic Activity in Myxoid Liposarcoma

Kerr

Donoghue

Wilding

et al. 2016

Sarcoma

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Myxoid liposarcoma is a rare form of soft-tissue sarcoma. Although most patients initially respond well to treatment, approximately 21% relapse, highlighting the need for alternative treatments. To identify novel treatment regimens and gain a better understanding of myxoid liposarcoma tumor biology, we screened various candidate and approved targeted therapeutics and chemotherapeutics against myxoid liposarcoma cell lines. Therapeutics that target angiogenesis showed antitumor activity. The small molecule inhibitor axitinib, which targets angiogenesis by inhibiting the VEGFR and PDGFR families and c-Kit, inhibited cell cycle progression and induced apoptosis in vitro, as well as having significant antitumor activity against MLS 1765 myxoid liposarcoma xenografts in mice. Axitinib also displayed synergistic antitumor activity in vitro when combined with the potassium channel ionophore salinomycin or the BH3 mimetic ABT-737. Another angiogenesis-targeting therapeutic, 4EGI-1, which targets the oncoprotein eIF4E, significantly decreased angiogenic ligand expression by myxoid liposarcoma cells and reduced tumor cell growth. To verify this oncogenic addiction to angiogenic pathways, we utilized VEGFR-derived ligand traps and found that autocrine VEGFR signaling was crucial to myxoid liposarcoma cell survival. Overall, these findings suggest that autocrine angiogenic signaling through the VEGFR family is critical to myxoid liposarcoma cell survival and that further study of axitinib as a potential anticancer therapy is warranted.

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Section: Discussionmentioning

confidence: 99%

Axitinib Has Antiangiogenic and Antitumorigenic Activity in Myxoid Liposarcoma

Kerr

Donoghue

Wilding

et al. 2016

Sarcoma

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Comparison of 18F-fluorodeoxyglucose PET/CT findings with vascular endothelial growth factors and receptors in colorectal cancer

et al. 2015

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The purpose of this study was to evaluate the association of (18)F-fluorodeoxyglucose (FDG)-PET/CT findings with the vascular endothelial growth factor (VEGF) family and its receptor (VEGFR) levels in metastatic and nonmetastatic colorectal cancer (CRC). Fluorine-18 FDG-PET/CT scans were performed for initial staging and restaging of patients with CRC. FDG-PET/CT findings of tumor (such as the presence of a primary tumor, the lymphatic or distance metastases, and the maximum standardized uptake value (SUVmax) of the primary tumor), serum VEGF A-C-D-E levels, and serum VEGF receptor 1-2-3 levels were analyzed. A total of 63 patients were included into the study (35 males, mean age 61.3 ± 11.9 years). Patients were divided into two groups, based on positive and negative PET/CT findings. Patients were also categorized according to the presence of metastasis. All evaluated parameters were significantly higher in the PET/CT-positive group than the PET/CT-negative group (p < 0.001). All those parameters were also positively correlated with each other. The highest correlation for SUVmax of primary tumor was found with VEGFR-3 (p < 0.001, r = 0.665). Patients with metastases had high levels of VEGF-D, VEGF-A, VEGF-C, VEGF-E, and VEGFR-3 than those without metastases. These parameters had better specificity and sensitivity values than the SUVmax of the primary tumor for detection of metastases. However, VEGF-D was the best indicator of metastasis in all of those parameters (VEGF-D vs SUVmax; sensitivity 100 vs 100 %; specificity 76 vs 76 %; AUC 0.903 vs 0.835; p < 0.001, respectively). Vascular endothelial growth factor family and its receptors were significantly higher in metastatic CRC patients. VEGF-D was the best indicator of metastasis than all VEGF family, VEGFR-3, and primary tumor SUVmax. VEGF family (A-C-D-E) and VEGFR-3 may help to determine the prognosis and management of CRC.

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Impact of the Prolymphangiogenic Crosstalk in the Tumor Microenvironment on Lymphatic Cancer Metastasis

Schlereth

Refaian

Iden

et al. 2014

BioMed Research International

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Lymphangiogenesis is a very early step in lymphatic metastasis. It is regulated and promoted not only by the tumor cells themselves, but also by cells of the tumor microenvironment, including cancer associated fibroblasts, mesenchymal stem cells, dendritic cells, or macrophages. Even the extracellular matrix as well as cytokines and growth factors are involved in the process of lymphangiogenesis and metastasis. The cellular and noncellular components influence each other and can be influenced by the tumor cells. The knowledge about mechanisms behind lymphangiogenesis in the tumor microenvironmental crosstalk is growing and offers starting points for new therapeutic approaches.

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Inhibiting tumor growth of colorectal cancer by blocking the expression of vascular endothelial growth factor receptor 3 using interference vector-based RNA interference

Cited by 7 publications

References 19 publications

Axitinib Has Antiangiogenic and Antitumorigenic Activity in Myxoid Liposarcoma

Axitinib Has Antiangiogenic and Antitumorigenic Activity in Myxoid Liposarcoma

Comparison of 18F-fluorodeoxyglucose PET/CT findings with vascular endothelial growth factors and receptors in colorectal cancer

Impact of the Prolymphangiogenic Crosstalk in the Tumor Microenvironment on Lymphatic Cancer Metastasis

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