Skip to main content
Top
Published in: Pathology & Oncology Research 3/2014

01-07-2014 | Research

HIF-1α Expression Correlates with Cellular Apoptosis, Angiogenesis and Clinical Prognosis in Rectal Carcinoma

Authors: Liu Feng, Lin Tao, He Dawei, Li Xuliang, Luo Xiaodong

Published in: Pathology & Oncology Research | Issue 3/2014

Login to get access

Abstract

Regional hypoxia caused by accelerated cell proliferation and overgrowth is an important characteristic of neoplasm. Hypoxia can cause a series of changes in gene transcription and protein expression, thereby not only inducing tumor cell resistance to radiotherapy and chemotherapy but also promoting tumor invasion and metastasis. This study aimed to investigate the relationship between HIF-1α expression and cellular apoptosis, angiogenesis and clinical prognosis in rectal carcinoma. In 113 rectal carcinoma cases, cellular apoptosis was analyzed by the in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, whereas the levels of HIF-1α expression, VEGF expression, microvessel density (MVD) and lymphatic vessel density(LVD) were examined by immunohistochemical staining. HIF-1 expression was detected in 67 of 113 rectal carcinoma cases (59.3 %). A positive correlation was found among HIF-1α expression, cellular apoptosis and angiogenesis. The 5-year survival rate in the HIF-1α-negative group was significantly higher than that in the HIF-1α-positive group (81.34 % versus 50 %, P < 0.05). According to the Cox regression analysis, HIF-1α expression, VEGF expression and cellular apoptosis index were independent risk factors for clinical prognosis in rectal carcinoma. Aberrant HIF-1α expression correlates with apoptosis inhibition, angiogenesis and poor prognosis in rectal carcinoma.
Literature
1.
go back to reference Gupta SC, Kim JH, Prasad S et al (2010) Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev 29(3):405–434PubMedCrossRefPubMedCentral Gupta SC, Kim JH, Prasad S et al (2010) Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev 29(3):405–434PubMedCrossRefPubMedCentral
2.
go back to reference de Krijger I, Mekenkamp LJ, Punt CJ et al (2011) MicroRNAs in colorectal cancer metastasis. J Pathol 224(4):438–447PubMedCrossRef de Krijger I, Mekenkamp LJ, Punt CJ et al (2011) MicroRNAs in colorectal cancer metastasis. J Pathol 224(4):438–447PubMedCrossRef
3.
go back to reference Arvelo F, Cotte C (2009) Hypoxia in cancer malignity. Invest Clin 50(4):529–546PubMed Arvelo F, Cotte C (2009) Hypoxia in cancer malignity. Invest Clin 50(4):529–546PubMed
4.
go back to reference Greijer AE, van der Groep P, Kemming D et al (2005) Up-regulation of gene expression by hypoxia is medi-ated predominantly by hypoxia-inducible factor 1 (HIF-1). J Pathol 206:291–304PubMedCrossRef Greijer AE, van der Groep P, Kemming D et al (2005) Up-regulation of gene expression by hypoxia is medi-ated predominantly by hypoxia-inducible factor 1 (HIF-1). J Pathol 206:291–304PubMedCrossRef
5.
go back to reference Belozerov VE, Van Meir EG (2005) Hypoxia inducible factor-1: a novel target for cancer therapy. Anticancer Drugs 16(9):901–909PubMedCrossRef Belozerov VE, Van Meir EG (2005) Hypoxia inducible factor-1: a novel target for cancer therapy. Anticancer Drugs 16(9):901–909PubMedCrossRef
6.
go back to reference Mucaj V, Shay JE, Simon MC (2012) Effects of hypoxia and HIFs on cancer metabolism. Int J Hematol 95(5):464–670PubMedCrossRef Mucaj V, Shay JE, Simon MC (2012) Effects of hypoxia and HIFs on cancer metabolism. Int J Hematol 95(5):464–670PubMedCrossRef
7.
go back to reference Semenza GL (2000) HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol 88(4):1474–1480PubMed Semenza GL (2000) HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol 88(4):1474–1480PubMed
8.
go back to reference Yeung SJ, Pan J, Lee MH (2008) Roles of p53, MYC and HIF-1 in regulating glycolysis - the seventh hallmark of cancer. Cell Mol Life Sci 65(24):3981–3999PubMedCrossRef Yeung SJ, Pan J, Lee MH (2008) Roles of p53, MYC and HIF-1 in regulating glycolysis - the seventh hallmark of cancer. Cell Mol Life Sci 65(24):3981–3999PubMedCrossRef
9.
go back to reference Rapisarda A, Melillo G (2012) Role of the VEGF/VEGFR axis in cancer biology and therapy. Adv Cancer Res 114:237–267PubMedCrossRef Rapisarda A, Melillo G (2012) Role of the VEGF/VEGFR axis in cancer biology and therapy. Adv Cancer Res 114:237–267PubMedCrossRef
12.
go back to reference Menrad H, Werno C, Schmid T et al (2010) Roles of hypoxia-inducible factor-1alpha (HIF-1alpha) versus HIF-2alpha in the survival of hepatocellular tumor spheroids. Hepatology 51(6):2183–2192PubMedCrossRef Menrad H, Werno C, Schmid T et al (2010) Roles of hypoxia-inducible factor-1alpha (HIF-1alpha) versus HIF-2alpha in the survival of hepatocellular tumor spheroids. Hepatology 51(6):2183–2192PubMedCrossRef
13.
go back to reference Ardyanto TD, Osaki M, Nagahama Y et al (2008) Down-regulation of cobalt-induced HIF-1alpha expression correlates with cell proliferation and apoptosis in human gastric carcinoma cells. Oncol Rep 19(2):339–343PubMed Ardyanto TD, Osaki M, Nagahama Y et al (2008) Down-regulation of cobalt-induced HIF-1alpha expression correlates with cell proliferation and apoptosis in human gastric carcinoma cells. Oncol Rep 19(2):339–343PubMed
14.
go back to reference Hao X, Du M, Bishop AE et al (1998) Imbalance between proliferation and apoptosis in development of colorectal carcinoma. Virchows Arch 433:523–527PubMedCrossRef Hao X, Du M, Bishop AE et al (1998) Imbalance between proliferation and apoptosis in development of colorectal carcinoma. Virchows Arch 433:523–527PubMedCrossRef
15.
go back to reference Benchabane H, Ahmed Y (2009) The adenomatous polyposis coli tumor suppressor and Wnt signaling in the regulation of apoptosis. Adv Exp Med Biol 656:75–84PubMedCrossRefPubMedCentral Benchabane H, Ahmed Y (2009) The adenomatous polyposis coli tumor suppressor and Wnt signaling in the regulation of apoptosis. Adv Exp Med Biol 656:75–84PubMedCrossRefPubMedCentral
16.
go back to reference Lampropoulos P, Zizi-Sermpetzoglou A, Rizos S et al (2012) TGF-beta signalling in colon carcinogenesis. Cancer Lett 314(1):1–7PubMedCrossRef Lampropoulos P, Zizi-Sermpetzoglou A, Rizos S et al (2012) TGF-beta signalling in colon carcinogenesis. Cancer Lett 314(1):1–7PubMedCrossRef
17.
go back to reference Liu W, Shen SM, Zhao XY et al (2012) Targeted genes and interacting proteins of hypoxia inducible factor-1. Int J Biochem Mol Biol 3(2):165–178PubMedPubMedCentral Liu W, Shen SM, Zhao XY et al (2012) Targeted genes and interacting proteins of hypoxia inducible factor-1. Int J Biochem Mol Biol 3(2):165–178PubMedPubMedCentral
18.
go back to reference Zhong H, De Marzo AM, Laughner E et al (1999) Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 59:5830–5835PubMed Zhong H, De Marzo AM, Laughner E et al (1999) Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 59:5830–5835PubMed
19.
go back to reference Koh MY, Spivak-Kroizman TR, Powis G (2010) HIF-1alpha and cancer therapy. Recent Results Cancer Res 180:15–34PubMedCrossRef Koh MY, Spivak-Kroizman TR, Powis G (2010) HIF-1alpha and cancer therapy. Recent Results Cancer Res 180:15–34PubMedCrossRef
20.
go back to reference Simiantonaki N, Taxeidis M, Jayasinghe C et al (2008) Hypoxia-inducible factor 1 alpha expression increases during colorectal carcinogenesis and tumor progression. BMC Cancer 8:320PubMedCrossRefPubMedCentral Simiantonaki N, Taxeidis M, Jayasinghe C et al (2008) Hypoxia-inducible factor 1 alpha expression increases during colorectal carcinogenesis and tumor progression. BMC Cancer 8:320PubMedCrossRefPubMedCentral
21.
go back to reference Kotch LE, Iyer NV, Laughner E et al (1999) Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death. Dev Biol 209:254–267PubMedCrossRef Kotch LE, Iyer NV, Laughner E et al (1999) Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death. Dev Biol 209:254–267PubMedCrossRef
22.
go back to reference Tsuzuki Y, Fukumura D, Oosthuyse B et al (2000) Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia-inducible factor-1alpha–> hypoxia re-sponse element–> VEGF cascade differentially regulates vascular response and growth rate in tumors. Cancer Res 60:6248–6252PubMed Tsuzuki Y, Fukumura D, Oosthuyse B et al (2000) Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia-inducible factor-1alpha–> hypoxia re-sponse element–> VEGF cascade differentially regulates vascular response and growth rate in tumors. Cancer Res 60:6248–6252PubMed
23.
25.
go back to reference Suzuki H, Tomida A, Tsuruo T (2001) Dephosphorylated hypoxia-inducible factor 1alpha as a mediator of p53-dependent apoptosis during hypoxia. Oncogene 20(41):5779–5788PubMedCrossRef Suzuki H, Tomida A, Tsuruo T (2001) Dephosphorylated hypoxia-inducible factor 1alpha as a mediator of p53-dependent apoptosis during hypoxia. Oncogene 20(41):5779–5788PubMedCrossRef
26.
go back to reference Piret JP, Mottet D, Raes M et al (2002) Is HIF-1alpha a pro- or an anti-apoptotic protein? Biochem Pharmacol 64(5–6):889–892PubMedCrossRef Piret JP, Mottet D, Raes M et al (2002) Is HIF-1alpha a pro- or an anti-apoptotic protein? Biochem Pharmacol 64(5–6):889–892PubMedCrossRef
27.
go back to reference Price DJ, Miralem T, Jiang S et al (2001) Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. Cell Growth Differ 12(3):129–135PubMed Price DJ, Miralem T, Jiang S et al (2001) Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. Cell Growth Differ 12(3):129–135PubMed
28.
go back to reference Bos R, van Diest PJ, van der Groep P et al (2004) Expression of hypoxia-inducible factor-1alpha and cell cycle proteins in invasive breast cancer are estrogen receptor related. Breast Cancer Res 6(4):R450–R459PubMedCrossRefPubMedCentral Bos R, van Diest PJ, van der Groep P et al (2004) Expression of hypoxia-inducible factor-1alpha and cell cycle proteins in invasive breast cancer are estrogen receptor related. Breast Cancer Res 6(4):R450–R459PubMedCrossRefPubMedCentral
29.
go back to reference Nagy JA, Vasile E, Feng D et al (2002) Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med 196(11):1497–1506PubMedCrossRefPubMedCentral Nagy JA, Vasile E, Feng D et al (2002) Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med 196(11):1497–1506PubMedCrossRefPubMedCentral
30.
go back to reference Mohammed RA, Green A, El-Shikh S et al (2007) Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. Br J Cancer 96(7):1092–1100PubMedCrossRefPubMedCentral Mohammed RA, Green A, El-Shikh S et al (2007) Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. Br J Cancer 96(7):1092–1100PubMedCrossRefPubMedCentral
31.
go back to reference Gao Y, Zhong WX, Mu DB et al (2008) Distributions of angiogenesis and lymphangiogenesis in gastrointestinal intramucosal tumors. Ann Surg Oncol 15(4):1117–1123PubMedCrossRef Gao Y, Zhong WX, Mu DB et al (2008) Distributions of angiogenesis and lymphangiogenesis in gastrointestinal intramucosal tumors. Ann Surg Oncol 15(4):1117–1123PubMedCrossRef
Metadata
Title
HIF-1α Expression Correlates with Cellular Apoptosis, Angiogenesis and Clinical Prognosis in Rectal Carcinoma
Authors
Liu Feng
Lin Tao
He Dawei
Li Xuliang
Luo Xiaodong
Publication date
01-07-2014
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 3/2014
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-013-9738-6

Other articles of this Issue 3/2014

Pathology & Oncology Research 3/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine