HIF-1-dependent Expression of Angiopoietin-like 4 and L1CAM Mediates Vascular Metastasis of Hypoxic Breast Cancer Cells to the Lungs

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2011 Aug 24

PMID 21860410

Citations 203

Authors

H Zhang

C C L Wong

H Wei

D M Gilkes

P Korangath

P Chaturvedi

L Schito

J Chen

B Krishnamachary

P T Winnard Jr

V Raman

L Zhen

W A Mitzner

S Sukumar

G L Semenza

Affiliations

Soon will be listed here.

Abstract

Most cases of breast cancer (BrCa) mortality are due to vascular metastasis. BrCa cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypoxia-inducible factor (HIF) activity in BrCa cells by RNA interference or digoxin treatment inhibits primary tumor growth and also inhibits the metastasis of BrCa cells to the lungs by blocking the expression of angiopoietin-like 4 (ANGPTL4) and L1 cell adhesion molecule (L1CAM). ANGPTL4 is a secreted factor that inhibits EC-EC interaction, whereas L1CAM increases the adherence of BrCa cells to ECs. Interference with HIF, ANGPTL4 or L1CAM expression inhibits vascular metastasis of BrCa cells to the lungs.

Citing Articles

The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering.

Zhu B, Xiang K, Li T, Li X, Shi F Cell Commun Signal. 2024; 22(1):512.

PMID: 39434182 PMC: 11492701. DOI: 10.1186/s12964-024-01870-w.

The interaction of platelet-related factors with tumor cells promotes tumor metastasis.

Xue J, Deng J, Qin H, Yan S, Zhao Z, Qin L J Transl Med. 2024; 22(1):371.

PMID: 38637802 PMC: 11025228. DOI: 10.1186/s12967-024-05126-6.

Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation.

Qannita R, Alalami A, Harb A, Aleidi S, Taneera J, Abu-Gharbieh E Pharmaceuticals (Basel). 2024; 17(2).

PMID: 38399410 PMC: 10892333. DOI: 10.3390/ph17020195.

Therapeutic Targeting of Hypoxia-Inducible Factors in Cancer.

Musleh Ud Din S, Streit S, Huynh B, Hana C, Abraham A, Hussein A Int J Mol Sci. 2024; 25(4).

PMID: 38396737 PMC: 10888675. DOI: 10.3390/ijms25042060.

Benzophenone-3 alters expression of genes encoding vascularization and epithelial-mesenchymal transition functions during Trp53-null mammary tumorigenesis.

Morozova E, Kariagina A, Busch C, Schwartz R Food Chem Toxicol. 2024; 186:114540.

PMID: 38387520 PMC: 10978255. DOI: 10.1016/j.fct.2024.114540.

References

Fukuda R, Zhang H, Kim J, Shimoda L, Dang C, Semenza G . HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell. 2007; 129(1):111-22. DOI: 10.1016/j.cell.2007.01.047. View

Erler J, Bennewith K, Cox T, Lang G, Bird D, Koong A . Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell. 2008; 15(1):35-44. PMC: 3050620. DOI: 10.1016/j.ccr.2008.11.012. View

Schindl M, Schoppmann S, Samonigg H, Hausmaninger H, Kwasny W, Gnant M . Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin Cancer Res. 2002; 8(6):1831-7. View

CAILLEAU R, Young R, Olive M, REEVES Jr W . Breast tumor cell lines from pleural effusions. J Natl Cancer Inst. 1974; 53(3):661-74. PMC: 7364228. DOI: 10.1093/jnci/53.3.661. View

Giatromanolaki A, Koukourakis M, Simopoulos C, Polychronidis A, Gatter K, Harris A . c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-1alpha dependent. Clin Cancer Res. 2004; 10(23):7972-7. DOI: 10.1158/1078-0432.CCR-04-1068. View

Gupta G, Nguyen D, Chiang A, Bos P, Kim J, Nadal C . Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature. 2007; 446(7137):765-70. DOI: 10.1038/nature05760. View

Erler J, Bennewith K, Nicolau M, Dornhofer N, Kong C, Le Q . Lysyl oxidase is essential for hypoxia-induced metastasis. Nature. 2006; 440(7088):1222-6. DOI: 10.1038/nature04695. View

Subarsky P, Hill R . The hypoxic tumour microenvironment and metastatic progression. Clin Exp Metastasis. 2003; 20(3):237-50. DOI: 10.1023/a:1022939318102. View

Melillo G . Targeting hypoxia cell signaling for cancer therapy. Cancer Metastasis Rev. 2007; 26(2):341-52. DOI: 10.1007/s10555-007-9059-x. View

10.

Padua D, Zhang X, Wang Q, Nadal C, Gerald W, Gomis R . TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell. 2008; 133(1):66-77. PMC: 2390892. DOI: 10.1016/j.cell.2008.01.046. View

11.

Liao D, Corle C, Seagroves T, Johnson R . Hypoxia-inducible factor-1alpha is a key regulator of metastasis in a transgenic model of cancer initiation and progression. Cancer Res. 2007; 67(2):563-72. DOI: 10.1158/0008-5472.CAN-06-2701. View

12.

Krishnamachary B, Zagzag D, Nagasawa H, Rainey K, Okuyama H, Baek J . Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B. Cancer Res. 2006; 66(5):2725-31. DOI: 10.1158/0008-5472.CAN-05-3719. View

13.

Buffa F, Harris A, West C, Miller C . Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene. Br J Cancer. 2010; 102(2):428-35. PMC: 2816644. DOI: 10.1038/sj.bjc.6605450. View

14.

Belanger A, Lu H, Date T, Liu L, Vincent K, Akita G . Hypoxia up-regulates expression of peroxisome proliferator-activated receptor gamma angiopoietin-related gene (PGAR) in cardiomyocytes: role of hypoxia inducible factor 1alpha. J Mol Cell Cardiol. 2002; 34(7):765-74. DOI: 10.1006/jmcc.2002.2021. View

15.

Vaupel P, Mayer A, Hockel M . Tumor hypoxia and malignant progression. Methods Enzymol. 2004; 381:335-54. DOI: 10.1016/S0076-6879(04)81023-1. View

16.

Minn A, Gupta G, Siegel P, Bos P, Shu W, Giri D . Genes that mediate breast cancer metastasis to lung. Nature. 2005; 436(7050):518-24. PMC: 1283098. DOI: 10.1038/nature03799. View

17.

Generali D, Berruti A, Brizzi M, Campo L, Bonardi S, Wigfield S . Hypoxia-inducible factor-1alpha expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer. Clin Cancer Res. 2006; 12(15):4562-8. DOI: 10.1158/1078-0432.CCR-05-2690. View

18.

Ueno M, Maeno T, Nomura M, Aoyagi-Ikeda K, Matsui H, Hara K . Hypoxia-inducible factor-1α mediates TGF-β-induced PAI-1 production in alveolar macrophages in pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2011; 300(5):L740-52. DOI: 10.1152/ajplung.00146.2010. View

19.

Wang G, Jiang B, Rue E, Semenza G . Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995; 92(12):5510-4. PMC: 41725. DOI: 10.1073/pnas.92.12.5510. View

20.

Bos R, van der Groep P, Greijer A, Shvarts A, Meijer S, Pinedo H . Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer. 2003; 97(6):1573-81. DOI: 10.1002/cncr.11246. View