Vascular endothelial growth factor is implicated in early invasion in cervical cancer

Kodama, Junichi; Seki, Nobuhiko; Tokumo, Keizo; Hongo, Atsushi; Miyagi, Yasunari; Yoshinouchi, Mitsuo; Okuda, Hiroyuki; Kudo, Takafumi

doi:10.1016/s0959-8049(98)00410-9

Cited by 65 publications

(42 citation statements)

References 30 publications

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“…VEGF stimulates endothelial cell proliferation, migration and tube formation [26]. In fact, tumor growth beyond 1 ± 2mm 3 which contributes to the metastatic process carrying cancer cells into the circulation is strictly dependent on angiogenesis [27]. The over expressed genes showed that A549 CD133 + cells had characters of angiogenesis which correlated with its ability of liver metastasis.…”

Section: Discussionmentioning

confidence: 99%

CD133 positive cells isolated from A549 cell line exhibited high liver metastatic potential

Zhang¹,

Yang²,

Sun³

et al. 2014

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Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapy. In present study, we identified a subpopulation of cells isolated from the A549 cell line with marker CD133. In vivo results showed that A549 CD133 + cells displayed high liver metastatic potential. Severe liver cell damage with tumor cell invasion revealed by pathological examination and these changes were consistent with the results of serological tests where the plasma GPT and GOT level are significantly higher than that of the control group. Compared with A549 cells, A549 CD133 + cells expressed high levels of VEGF and exhibited high migration and invasion capability. In conclusion, we first reported that A549 CD133 + cells exhibited characteristic of high liver metastatic potential which makes it be a suitable model for further study of liver metastasis of lung adenocarcinoma and provide a potential platform for antimetastatic drug discovery or evaluation. Key words: human lung adenocarcinoma, liver metastasis, migration, invasion, CD133Lung cancer is one of the most aggressive neoplasms in the world [1]. Despite management and treatment of lung cancer has been improved these years, but the prognosis remains poor, the 5-year survival rate of non-small cell lung cancer (NSCLC) is no more than 15 % [2]. Approximately 50 % of NSCLC patients with stage I and II will die from recurrent disease despite conventional therapy, and nearly 70% of lung cancer patients will die from metastatic disease, even after surgical resection of the primary tumor, radiation therapy, and chemotherapy [3]. Thus, it is important to find novel effective therapies to inhibit lung cancer metastasis.The most common four metastatic sites of patients with solitary metastatic NSCLC were: bone, liver, kidney and spleen [3]. Nevertheless, the mechanism of which lung adenocarcinoma selectively disseminated to certain organs remains unknown. However, experimental reproducible animal models facilitate to understand the process of metastasis and can provide suitable models for basic or preclinical studies.Different kinds of cancer metastasis model have been published yet. Early in 1996, Iguchi H et al [4] have established lung cancer metastasis model with human lung squamous cell carcinoma-derived cells (HARA). In 1959, Leduc [5] was the first to describe liver metastasis in mice after injection of hepatoma carcinoma cells in the spleen. Moreover, the liver metastasis models in nude mice of colon carcinoma have been successfully established [6,7]. Early studies in immunodeficient mice illustrated that subcutaneous injection of tumor cells seldom give rise to liver metastases [8].However, no lung adenocarcinoma liver metastasis model has been published so far. CD133 as a marker of cancer stem cells (CSCs) has been demonstrated in many cancers including lung cancer [9][10][11][12][13]. The CSCs theory indicated that subpopulation of tumor cells with stem or progenitor cell characteristics c...

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Section: Discussionmentioning

confidence: 99%

CD133 positive cells isolated from A549 cell line exhibited high liver metastatic potential

Zhang¹,

Yang²,

Sun³

et al. 2014

neo

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“…VEGF is a potent angiogenic factor that is pivotal in the transition from an avascular tumor to a vascularizing phenotype tumor (Ferrara and Davis-Smyth, 1997). VEGF expression has been reported to be associated with the progression of cervical intraepithelial neoplasia (Guidi et al, 1995;Dobbs et al, 1997), the angiogenesis and early invasion of cervical cancer, and the prognosis of patients with early-stage cervical cancer (Kodama et al, 1999;Cheng et al, 2000). Given the importance of VEGF in the development of cervical cancer, clarifying the cellular factors responsible for its regulation may provide molecular therapeutic targets for cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 promotes cervical tumor growth by VEGF-dependent angiogenesis via a STAT3 pathway

et al. 2003

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“…Total RNA (1 mg) from infected or mock-infected keratinocytes was reversed transcribed and the cDNA amplified by PCR using primers specific for VEGF. The primers used recognize four isoforms of VEGF (Kodama et al, 1999). The reactions were stopped after 18 and 22 cycles and product was visualized on a 1% EtBr stained agarose gel.…”

Section: Discussionmentioning

confidence: 99%

Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors

2004

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Human papillomavirus (HPV) 16 is involved in causing cervical cancer. The E6 and E7 proteins of HPV 16 immortalize human keratinocytes and this is due, at least in part, to inactivation of the tumor suppressor proteins p53 and pRB. These tumor suppressor proteins also regulate the expression of pro-and antiangiogenic factors by cells. For this reason, experiments were conducted to determine whether the expression of E6 and E7 in primary keratinocytes alters the phenotype of these cells such that they express diminished levels of antiangiogenic factors and/or increased levels of proangiogenic factors. To avoid variances in experimental observations, pools of human foreskin keratinocytes from multiple sources were infected with recombinant retrovirus expressing HPV 16 E6 and E7 or control retrovirus. Gene array analysis, RT-PCR, ELISAs and Western blotting showed that in cells expressing HPV 16 E6 and E7, expression levels of two potent angiogenesis inhibitors, thrombospondin-1 and maspin, were lower compared to controls. Additionally, major angiogenesis inducers, interleukin-8 and vascular endothelial growth factor (VEGF), were increased relative to controls. VEGF can be produced as multiple splice variants, all of which are required for the formation of patent blood vessels. The expression of HPV 16 E6 and E7 in keratinocytes augmented expression of VEGF 121, 145, 165 and 189. These observations show that HPV 16 E6 and E7 alter the phenotype of primary keratinocytes, diminishing expression of inhibitors and increasing expression of inducers of angiogenesis. This altered phenotype may permit keratinocytes infected by HPV 16 to play a role in the progression of cancer by permitting tumors to acquire a blood supply permissive of growth and spread.

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Vascular endothelial growth factor is implicated in early invasion in cervical cancer

Cited by 65 publications

References 30 publications

CD133 positive cells isolated from A549 cell line exhibited high liver metastatic potential

CD133 positive cells isolated from A549 cell line exhibited high liver metastatic potential

Interleukin-6 promotes cervical tumor growth by VEGF-dependent angiogenesis via a STAT3 pathway

Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors

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