Overexpression of Lymphangiogenic Growth Factor VEGF-C in Human Pancreatic Cancer

Tang, Rui; Itakura, Jun; Aikawa, Takuma; Matsuda, Kei; Fujii, Hideki; Korc, Murray; Matsumoto, Yoshirô

doi:10.1097/00006676-200104000-00010

Cited by 78 publications

(49 citation statements)

References 27 publications

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“…A positive association of VEGF-C expression with lymph node metastasis has been reported in head and neck cancer, thyroid cancer, lung cancer, oesophageal cancer, pancreatic cancer, gastric cancer, colorectal cancer, ovarian cancer and prostatic cancer (Bunone et al, 1999;Tsurusaki et al, 1999;Yonemura et al, 1999;Kajita et al, 2001;Kitadai et al, 2001;Tang et al, 2001;Kawakami et al, 2003;Neuchrist et al, 2003;Yokoyama et al, 2003). However, some types of cancer, including lung cancer, did not demonstrate a positive association of VEGF-C with lymph node metastasis (Arinaga et al, 2003;van Trappen et al, 2003;Ogawa et al, 2004).…”

Section: Discussionmentioning

confidence: 96%

The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer

et al. 2006

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A positive association between vascular endothelial growth factor-C (VEGF-C) expression and lymph node metastasis has been reported in several cancers. However, the relationship of VEGF-C and lymph node metastasis in some cancers, including non-small cell lung cancer (NSCLC), is controversial. We evaluated the VEGF-C and vascular endothelial growth factor receptor-3 (VEGFR-3) expression in NSCLC samples from patients who had undergone surgery between 1998 and 2002 using real-time quantitative RT–PCR and immunohistochemical staining. We failed to find a positive association between VEGF-C and VEGFR-3 mRNA expression and lymph node metastasis in NSCLC. An immunohistological study demonstrated that VEGF-C was expressed not only in cancer cells, but also in macrophages in NSCLC, and that VEGFR-3 was expressed in cancer cells, macrophages, type II pneumocytes and lymph vessels. The VEGF-C/VEGFR-3 ratio of the node-positive group was significantly higher than that of the node-negative group. Immunohistochemical staining showed that VEGFR-3 was mainly expressed in cancer cells. The immunoreactivity of VEGF-C and VEGFR-3 was roughly correlated to the mRNA levels of VEGF-C and VEGFR-3 in real-time PCR. VEGF-C mRNA alone has no positive association with lymph node metastasis in NSCLC. The VEGF-C/VEGFR-3 ratio was positively associated with lymph node metastasis in NSCLC. This suggests that VEGF-C promotes lymph node metastasis while being influenced by the strength of the VEGF-C autocrine loop, and the VEGF-C/VEGFR-3 ratio can be a useful predictor of lymph node metastasis in NSCLC.

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Section: Discussionmentioning

confidence: 96%

The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer

et al. 2006

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“…Published work on lymphangiogenesis in pancreatic cancer has identified VEGF-C and VEGF-D as important stimulators (Tang et al, 2001;von Marschall et al, 2005) prompting us to test the effects of p16 induction on the amount of VEGF-C or -D produced in MiaPaca-2-TREx-p16 cells in vitro. However, neither of these two VEGF family members were found regulated, suggesting that additional factors controlled lymphangiogenesis in MiaPaca-2-TREx-p16 tumours.…”

Section: Discussionmentioning

confidence: 99%

Inducible re-expression of p16 in an orthotopic mouse model of pancreatic cancer inhibits lymphangiogenesis and lymphatic metastasis

et al. 2008

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Functional inactivation of the tumour suppressor protein p16 INK4a constitutes a key event in the multistep process of pancreatic ductal cell transformation. However, the significance of p16 inactivation for complex and tissue-specific aspects of pancreatic cancer progression, such as angiogenesis and metastasis, is less understood. Here, we inducibly re-expressed p16 in vivo in an orthotopic model of pancreatic cancer and examined the impact on these clinically relevant aspects of pancreatic cancer tumour biology. Consistent with previous work in subcutaneous xenograft models, we found p16 capable of reducing primary tumour growth. In addition, p16 restitution resulted in a marked reduction of tumour angiogenesis, largely accounted for by a p16-dependent inhibition of lymphangiogenesis. In excellent agreement with the antilymphangiogenic effect, re-expression of p16 almost completely prevented lymph node metastases of MiaPaca-2 pancreatic tumours. To our knowledge, this is the first report that experimentally links the tumour suppressor p16 to the process of lymphangiogenesis.

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“…Immunohistochemical analysis confirmed the expression of VEGF-C and its receptor (VEGFR-3) in the cancer cells within the tumor mass. VEGF-C expression was positive in approximately 80% of pancreatic cancers [86,84]. VEGF-C was abundantly expressed in pancreatic cancer tissue and cell lines and VEGFR-3 was expressed in cancer stromal cells.…”

Section: Pancreatic Cancermentioning

confidence: 98%

“…Moreover, in human pancreatic cancer and nude mice model, the expression of VEGF-C on lymphatic metastasis was higher than in primary tumor [89]. The presence of VEGF-C in the cancer cells was associated with increased lymph node metastasis, but it was not associated with decreased patient survival [86,82].…”

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

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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.

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Overexpression of Lymphangiogenic Growth Factor VEGF-C in Human Pancreatic Cancer

Cited by 78 publications

References 27 publications

The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer

The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer

Inducible re-expression of p16 in an orthotopic mouse model of pancreatic cancer inhibits lymphangiogenesis and lymphatic metastasis

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

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