Dataset Information

In vitro angiogenesis and expression of nuclear factor kappaB and VEGF in high and low metastasis cell lines of salivary gland Adenoid Cystic Carcinoma.

ABSTRACT:

Background

Adenoid cystic carcinoma is a high malignant carcinoma characterized by intensive local invasion and high incidence of distant metastasis. Although many reports have demonstrated that angiogenesis has played an important role in tumor metastasis, the relationship between metastasis characters and angiogenesis ability in high and low metastasis cell lines of Adenoid cystic carcinoma has rarely been reported. The present study aimed to compare the angiogenesis ability of ACC-M (high metastasis) and ACC-2 (low metastasis) cell lines in vitro. Furthermore, the activity of nuclear factor kappaappa B and the expression of vascular endothelial growth factor (VEGF) in ACC-2 and ACC-M were also detected.

Methods

Electrophoretic mobility shift assay was used to detect nuclear factor kappaappa B activity. Semi-quantitative RT-PCR was used to quantify the mRNA level of VEGF. Immuofluorescence double staining and semi-quantitative confocal laser scanning analysis was carried out to detect nuclear factor kappaappa B nuclear localization and staining intensity of VEGF. The angiogenesis ability of ACC-M and ACC-2 was compared by an in vitro three-dimensional angiogenic model assay. The vector transfection assay was performed to transfect the PCMV-IkappaBalphaM vector into ACCs cell lines expressing the phosphorylation defective IkappaBalphaM.

Results

Nuclear factor kappaappa B activity and the rate of nuclear factor kappaappa B nuclear localization in ACC-M was significantly higher than that in ACC-2. Moreover, ACC-M exhibited higher mRNA and protein levels of vascular endothelial growth factor than ACC-2. VEGF mRNA expression was effectively decreased by inhibition of nuclear factor kappaappa B activity. Furthermore, ACC-M could remarkably stimulate the migration and tube formation of endothelial cells and induce The umbilical vein endothelial cells sprouting into the gel matrix.

Conclusion

These results implicated that ACCs cells with higher metastasis feature might present greater angiogenesis ability.

SUBMITTER: Zhang J

PROVIDER: S-EPMC1903362 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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Publications

In vitro angiogenesis and expression of nuclear factor kappaB and VEGF in high and low metastasis cell lines of salivary gland Adenoid Cystic Carcinoma.

Zhang Jiali J Peng Bin B

BMC cancer 20070601

<h4>Background</h4>Adenoid cystic carcinoma is a high malignant carcinoma characterized by intensive local invasion and high incidence of distant metastasis. Although many reports have demonstrated that angiogenesis has played an important role in tumor metastasis, the relationship between metastasis characters and angiogenesis ability in high and low metastasis cell lines of Adenoid cystic carcinoma has rarely been reported. The present study aimed to compare the angiogenesis ability of ACC-M ( ...[more]

PMID: 17543095

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Project description:Adenoid cystic carcinoma (ACC) is a slow growing, but relentless cancer. Due to its rarity and lack of understanding of its molecular etiology, no standard chemotherapy for ACC currently exists and many patients suffer from recurrent and/or metastatic disease. As such, development of safe and effective therapies is imperative. To describe and summarize existing clinical trial studies and preclinical discoveries, we surveyed the PubMed on developmental therapeutics for ACC. Objective response rates to monotherapy with cytotoxic agents were approximately 10% with cisplatin, 5-FU, gemcitabine, mitoxantrone, epirubicin, vinorelbine and paclitaxel. The most studied combination therapies were cyclophosphamide-doxorubicin-cisplatin (CAP) and cisplatin-vinorelbine, with an objective response rate of 18-31%. Among molecularly targeted drugs, the most studied drugs are inhibitors targeting the vascular endothelial growth factor receptor (VEGFR) to inhibit tumor angiogenesis. Among those, lenvatinib and axitinib showed a relatively high objective response rate of 11-16% and 9-17%, respectively. Given high recurrence rates and chemoresistance of ACC, treatments targeting cancer stem cells (CSC), which function as tumor-initiating cells and drive chemoresistance, may be particularly valuable. CSC have been shown to be targetable via MYB, Notch1, p53 and epigenetic mechanisms. Myb overexpression is characteristic in ACC but was previously thought to present a difficult target due to its nature as a transcription factor. However, due to the development Myb-targeted inhibitors and an ongoing clinical trial of MYB-targeted cancer vaccine therapy, MYB is becoming an increasingly attractive therapeutic target. Drugs targeting NOTCH signaling demonstrated 5-17% response rate in phase I clinical trials. Within the field of epigenetics, treatment with PRMT5 inhibitors has shown 21% partial response rate in phase I clinical trial. Immunotherapies, such as PD-1 inhibitors, are also associated with CSC, but have not been effective against ACC. However, clinical trials of cancer vaccine therapies are actively being conducted. In addition to conventional chemotherapies and inhibitors of angiogenesis, the emergence of new therapies such as immunotherapy and those targeting cancer stemness is expected to bring clinical benefits to patients in the future.

Dataset Information

In vitro angiogenesis and expression of nuclear factor kappaB and VEGF in high and low metastasis cell lines of salivary gland Adenoid Cystic Carcinoma.

Background

Methods

Results

Conclusion

Publications

In vitro angiogenesis and expression of nuclear factor kappaB and VEGF in high and low metastasis cell lines of salivary gland Adenoid Cystic Carcinoma.

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