Expression of VEGF-C and LYVE-1 in Breast Cancer Tissues

Hu-An Chun; Byung-Ho Son; Beom Seok Kwak; Sei Hyun Ahn; Gyung Yub Gong; Ho Sung Yoon

doi:10.4048/jbc.2006.9.1.47

Journal List > J Breast Cancer > v.9(1) > 1036811

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Chun, Son, Kwak, Ahn, Gong, and Yoon: Expression of VEGF-C and LYVE-1 in Breast Cancer Tissues

Original Article

Journal of Breast Cancer

Journal of Breast Cancer 2006; 9(1): 47-54.

Published online: 31 March 2006

DOI: https://doi.org/10.4048/jbc.2006.9.1.47

Expression of VEGF-C and LYVE-1 in Breast Cancer Tissues

Hu-An Chun, Byung-Ho Son, Beom Seok Kwak, Sei Hyun Ahn, Gyung Yub Gong, Ho Sung Yoon

Department of Surgery, University of Hanyang, College of Medicine Hanyang University Hospital, Seoul, Korea.

Corresponding author (yoonhs@hanyang ac.kr)

Received 2 January 2006 Accepted 17 February 2006

Abstract

Purpose

The aim of this study was to assess the expression of VEGF-C (vascular endothelial growth factor-C) and LYVE-1 (lymphatic vessel endothelial HA receptor-1) mRNA in human breast cancer, and to compare the expression of VEGF-C protein and VEGF-C, LYVE-1 mRNA with the clinico-pathological outcomes.

Methods

RT-PCR was carried on the VEGF-C, LYVE-1 mRNA drawn from three samples of adjacent normal breast tissues, the MCF-7 breast cancer cell line and 39 breast cancer tissues. Immunohistochemical staining was done to detect the expression of VEGF-C protein in 39 cancer tissues and in 5 benign tissues with using well preserved, paraffin embedded tissues. The clinicopathological findings were retrospectively reviewed for menopausal status, lymphatic invasion, hormonal status, the expression of p53 and c-erbB2.

Results

RT-PCR analysis revealed the expression of VEGF-C mRNA in 22 of 39 (56.4%) and LYVE-1 mRNA in 19 of 39 breast cancer tissues (48.7%). The expression of VEGF-C mRNA was positive in all cases except for one in LYVE-1 mRNA positive case, this revealed good correlation between the two molecules. Immunohistochemical analysis revealed that VEGF-C protein was expressed only in the breast cancer cells, with specific VEGF-C staining evident in 10 of 39 (25.6%). There was no significant correlation between VEGF-C, LYVE-1 mRNA expressions and the other pathologic variables. However, VEGF-C protein expression was negative in the group with a postmenopausal status, positive estrogen receptor and negative c-erbB2 significantly.

Conclusions

VEGF-C mRNA seems to be related to the lymphangiogenetic marker-LYVE-1 mRNA and the amplification of the VEGF-C may be correlated with some clinico-pathological factors in the breast cancer.

Keywords: Breast cancer, VEGF-C, LYVE-1

References

1. Korean Breast Cancer Society. Nationwide Korean Breast Cancer Data of 2002. J Korean Breast Cancer Soc. 2002. 5:217–224.

2. Ruoslahti E. How cancer spreads. Sci Am. 1996. 275:72–77.

3. Albertini JJ, Lyman GH, Cox C, Yeatman T, Balducci L, Ku N, et al. Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA. 1996. 276:1818–1822.

4. Kato T, Kimura T, Miyakawa R, Tanaka S, Fujii A, Yamamoto K, et al. clinicopathologic study of angiogenesis in Japanese patients with breast cancer. World J Surg. 1997. 21:49–56.

5. Lauria R, Perrone F, Carlomagno C, De Laurentiis M, Morabito A, Gallo C, et al. The prognostic value of lymphatic and blood vessel invasion in operable breast cancer. Cancer. 1995. 76:1772–1778.

6. Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, et al. LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol. 1999. 44:789–801.

7. Nathanson SD. Insights into the mechanism of lymph node metastasis. Cancer. 2003. 98:413–423.

8. Ferrara N. Vascular endothelial growth factors and the regulation of angiogenesis. Recent Prog Horm Res. 2000. 55:15–35.

9. Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, et al. A novel vascular endothelial growth factor, VEGF-C is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 1996. 15:290–298.

10. Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001. 7:192–198.

11. Olofsson B, Jeltsch M, Ericsson U, Alitalo K. Current biology of VEGF-B and VEGF-C. Curr Opin Biotechnol. 1999. 10:528–535.

12. Lee SC, Song SH, Kim SW, Kim JH, Yun SS, Choi JH, et al. Vascular endothelial growth factor (VEGF) expression and angiogenesis in gastric cancer. J Korean Surg Soc. 2001. 60:288–296.

13. Hoar Fj, Chaudhri S, Wadley MS, Stonelake PS. Co-expression of vascular endothelial growth factor C (VEGF-C) and c-erbB2 in human breast carcinoma. Eur J Cancer. 2003. 39:1698–1703.

14. Kinoshita J, Kitamura K, Kabashima A, Saeki H, Tanaka S, Sugimachi K. Clinical significance of vascular endothelial growth factor-C (VEGF-C) in breast cancer. Breast Cancer Res Treat. 2001. 66:159–164.

15. Nakamura Y, Yasuoka H, Tsujimoto M, Yang Q, Tsukiyama A, Imabun S, et al. Clinicopathological significance of vascular endothelial growth factor-C in breast carcinoma with long term follow-up. Mod Pathol. 2003. 16:309–314.

16. Niki T, Iba S, Tokunou M, Yamada T, Matsuno Y, Hirohashi S. Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma. Clin Cancer Res. 2000. 6:2431–2439.

17. Hashimoto I, Kodama J, Seki N, Hongo A, Yoshinouchi M, Okuda H, et al. Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer. Br J Cancer. 2001. 85:93–97.

18. Yang W, Klos K, Yang Y, Smith TL, Shi D, Yu D. ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma. Cancer. 2002. 94:2855–2861.

19. Gunningham SP, Currie MJ, Han C, Robison BA, Scott PA, Harris AL, et al. The short form of the alternatively spliced flt-4 but not its ligand vascular endothelial growth factor C is related to lymph node metastasis in human breast cancers. Clin Cancer Res. 2000. 6:4278–4286.

20. Scott PA, Smith K, Poulsom R, Benedetti AD, Bicknell R, Harris AL. Differential expression of vascular endothelial growth factor mRNA vs protein isoform expression in human breast cancer and relationship to eIF-4E. Br J Cancer. 1998. 77:2120–2128.

21. Cunnick GH, Jiang WG, Gomez KF, Mansel RE. Lymphangiogenesis quantification using quantitative PCR and breast cancer as a model. Biochem Biophys Res Commn. 2001. 288:1043–1046.

22. Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990. 61:1303–1313.

23. Parr C, Jiang WG. Quantitative analysis of lymaphangiogenic markers in human colorectal cancer. Int J Oncol. 2003. 23:533–539.

24. Mandriota SJ, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J. 2001. 20:672–682.

25. Kajita T, Ohta Y, Kimura K, Tamura M, Tanaka Y, Tsunezuka Y, et al. The expression of vascular endothelial growth factor C and its receptors in non small cell lung cancer. Br J Cancer. 2001. 85:255–260.

26. Ruohola JK, Valve EM, Karkkainen MJ, Joukov V, Alitalo K, Harkonen PL. Vascular endothelial growth factors are differentially regulated by steroid hormones and antiestrogens in breast cancer cells. Mol Cell Endocrinol. 1999. 149:29–40.

TOOLS

Similar articles