The Akt expression correlates with the VEGF-A and -C expression as well as the microvessel and lymphatic vessel density in breast cancer

Oncology Reports

Volumn 23, Issue 3, 2010, Pages 621-630

  Tsutsui, Shinichi ^a   Matsuyama, Ayumi ^a   Yamamoto, Manabu ^a   Takeuchi, Hideya ^b   Oshiro, Yumi ^c   Ishida, Teruyoshi ^a   Maehara, Yoshihiko ^d  

^a ATOMIC BOMB SURVIVORS HOSPITAL   (Japan)

^b NATIONAL HOSPITAL ORGANIZATION BEPPU MEDICAL CENTER   (Japan)

^c MATSUYAMA RED CROSS HOSPITAL   (Japan)

^d KYUSHU UNIVERSITY   (Japan)

Author keywords

Akt; Breast cancer; Lymphatic vessel density; Microvessel density; VEGF A; VEGF C

Indexed keywords

PROTEIN KINASE B; VASCULOTROPIN A; VASCULOTROPIN C;

ADULT; AGED; ARTICLE; BREAST CANCER; CANCER RISK; CANCER SURVIVAL; DISEASE FREE SURVIVAL; FEMALE; HUMAN; LYMPH NODE METASTASIS; LYMPH VESSEL; MAJOR CLINICAL STUDY; MICROVASCULATURE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TUMOR VOLUME;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ADULT; AGED; AGED, 80 AND OVER; BREAST NEOPLASMS; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; IMMUNOHISTOCHEMISTRY; LYMPHANGIOGENESIS; LYMPHATIC METASTASIS; LYMPHATIC VESSELS; MIDDLE AGED; PROTO-ONCOGENE PROTEINS C-AKT; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR C;

EID: 77349127052     PISSN: 1021335X     EISSN: 17912431     Source Type: Journal    
DOI: 10.3892/or_00000677     Document Type: Article

References (74)

1. Hanahan D and Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353-364, 1996.
2. Tsutsui S, Kume M and Era S: Prognostic value of microvessel density in invasive ductal carcinoma of the breast. Breast Cancer 10: 312-319, 2003.
3. Tsutsui S, Yasuda K, Suzuki K, Tahara K, Higashi H and Era S: Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density. Oncol Rep 14: 425-431, 2005.
4. Tsutsui S, Inoue H, Yasuda K, et al: Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel density. Breast Cancer Res Treat 98: 261-266, 2006.
5. Tsutsui S, Ohno S, Murakami S, Hachitanda Y and Oda S: Prognostic value of epidermal growth factor receptor (EGFR) and its relationship to the estrogen receptor status in 1029 patients with breast cancer. Breast Cancer Res Treat 71: 67-75, 2002.
6. Tsutsui S, Inoue H, Yasuda K, et al: Inactivation of PTEN is associated with a low p27kip1 protein expression in breast carcinoma. Cancer 104: 2048-2053, 2005.
7. Tsutsui S, Yasuda K, Suzuki K, et al: A loss of c-kit expression is associated with an advanced stage and poor prognosis in breast cancer. Br J Cancer 94: 1874-1878, 2006.
8. Van der Auwera I, Cao Y, Tille JC, et al: First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours. Br J Cancer 95: 1611-1625, 2006.
9. Kahn HJ and Marks A: A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors. Lab Invest 82: 1255-1257, 2002.
10. Schacht V, Dadras SS, Johnson LA, Jackson DG, Hong YK and Detmar M: Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. Am J Pathol 166: 913-921, 2005.
11. Joukov V, Pajusola K, Kaipainen A, 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 15: 290-298, 1996.
12. Scavelli C, Vacca A, Di Pietro G, Dammacco F and Ribatti D: Crosstalk between angiogenesis and lymphangiogenesis in tumor progression. Leukemia 18: 1054-1058, 2004.
13. Manning BD and Cantley LC: AKT/PKB signaling: navigating downstream. Cell 129: 1261-1274, 2007.
14. Jiang B and Liu L: PI3K/PTEN signaling in tumorigenesis and angiogenesis. Biochim Biophys Acta 1784: 150-158, 2008.
15. Bellacosa A, Testa JR, Staal SP and Tsichlis PN: A retroviral oncogne, akt, encoding a serine-threonine kinase containing as SH2-like region. Science 254: 274-277, 1991.
16. Perez-Tenorio G and Stal O: Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer 86: 540-545, 2002.
17. Schmitz KJ, Otterbach F, Gallies R, et al: Prognostic relevance of activated Akt kinase in node-negative breast cancer: a clinicopathological study of 99 cases. Mod Pathol 17: 15-21, 2004.
18. Mazure NM, Chen EY, Laderoute KR and Giaccia AJ: Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element. Blood 90: 3322-3331, 1997.
19. Jiang B, Zheng JZ, Aoki M and Vogt PK: Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc Natl Acad Sci USA 97: 1749-1753, 2000.
20. Dong G, Chen Z, Li Z, Yeh NT, Bancroft CC and van Waes C: Hepatocyte growth factor/scatter factor-induced activation of MEK and PI3K signal pathways contributes to expression of proangiogenic cytokines interleukin-8 and vascular endothelial growth factor in head and neck squamous cell carcinoma. Cancer Res 61: 5911-5918, 2001.
21. Skinner HD, Zheng JZ, Fang J, Agani F and Jiang B: Vascular endothelial growth factor transcriptional activation is mediated by hypoxia-inducible factor 1α, HDM2 and p70S6K1 in response to phosphatidylinositol 3-kinase/Akt signaling. J Biol Chem 279: 45643-45651, 2004.
22. Cao Z, Fang J, Xia C, Shi X and Jiang B: Trans-3,4,5'-trihydroxystibene inhibits hypoxia-inducible factor 1α and vascular endothelial growth factor expression in human ovarian cancer cells. Clin Cancer Res 10: 5253-5263, 2004.
23. Fang J, Xia C, Cao Z, Zheng JZ, Reed E and Jiang B: Apigenin inhibits VEGF and HIF-1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways. FASEB J 19: 342-353, 2005.
24. Zhong H, Chiles K, Feldser D, et al: Modulation of hypoxiainducible factor 1α expression by the epidermal growth factor/ phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res 60: 1541-1545, 2000.
25. Jiang B, Jiang G, Zheng JZ, Lu Z, Hunter T and Vogt PK: Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ 12: 363-369, 2001.
26. Tang Y, Zhang D, Fallavollita L and Brodt P: Vascular endothelial growth factor C expression and lymph node metastasis are regulated by the type I insulin-like growth factor receptor. Cancer Res 63: 1166-1171, 2003.
27. Kobayashi S, Kishimoto T, Kamata S, Otsuka M, Miyazaki M and Ishikura H: Rapamycin, a specific inhibitor of the mammalian target of rapamycin, suppresses lymphangiogenesis and lymphatic metastasis. Cancer Sci 98: 726-733, 2007.
28. Volm M, Koomagi R and Mattern J: Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squamous cell lung cancer. Int J Cancer 74: 64-68, 1997.
29. Skobe M, Hawighorst T, Jackson DG, et al: Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med 7: 192-198, 2001.
30. Mattila MM, Ruohola JK, Karpanen T, Jackson DG, Alitalo K and Harkonen PL: VEGF-C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF-7 tumors. Int J Cancer 98: 946-951, 2002.
31. Karpanen T, Egeblad M, Karkkainen MJ, et al: Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res 61: 1786-1790, 2001.
32. Vleugel MM, Bos R, van der Groep P, et al: Lack of lymphangiogenesis during breast carcinogenesis. J Clin Pathol 57: 746-751, 2004.
33. Williams CS, Leek RD, Robson AM, et al: Absence of lymphangiogenesis and intratumoural lymph vessels in human metastatic breast cancer. J Pathol 200: 195-206, 2003.
34. Agarwal B, Saxena R, Morimiya A, Mehrotra S and Badve S: Lymphangiogenesis does not occur in breast cancer. Am J Surg Pathol 29: 1449-1455, 2005.
35. Van der Auwera I, Colpaert C, van Marck E, Vermeulen P and Dirix L: Lymphangiogenesis in breast cancer. Am J Surg Pathol 30: 1055-1056, 2006.
36. Padera TP, Kadambi A, Di Tomaso E, et al: Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 296: 1883-1886, 2002.
37. Bono P, Wasenius VM, Heikkila P, Lundin J, Jackson DG and Joensuu H: High LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer. Clin Cancer Res 10: 7144-7149, 2004.
38. Schoppmann SF, Bayer G, Aumayr K, et al: Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive breast cancer. Ann Surg 240: 306-312, 2004.
39. Schoppmann SF, Fenzl A, Nagy K, et al: VEGF-C expressing tumor-associated macrophages in lymph node positive breast cancer: impact on lymphangiogenesis and survival. Surgery 139: 839-846, 2006.
40. Sedivy R, Beck-Mannagetta J, Haverkampf C, Battistutti W and Honigschnabl S: Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancer. J Oral Pathol Med 32: 455-460, 2003.
41. Hachisuka T, Narikiyo M, Yamada Y, et al: High lymphatic vessel density correlates with overexpression of VEGF-C in gastric cancer. Oncol Rep 13: 733-737, 2005.
42. Ohno M, Nakamura T, Kunimoto Y, Nishimura K, Chung-Kang C and Kuroda Y: Lymphangiogenesis correlates with expression of vascular endothelial growth factor-C in colorectal cancer. Oncol Rep 10: 939-943, 2003.
43. Renyi-Vamos F, Tovari J, Fillinger J, et al: Lymphangiogenesis correlates with lymph node metastasis, prognosis, and angiogenic phenotype in human non-small cell lung cancer. Clin Cancer Res 11: 7344-7353, 2005.
44. Nakamura Y, Yasuoka H, Tsujimoto M, et al: Lymph vessel density correlates with nodal status, VEGF-C expression, and prognosis in breast cancer. Breast Cancer Res Treat 91: 125-132, 2005.
45. Ueda M, Hung YC, Terai Y, et al: Vascular endothelial growth factor-C expression and invasive phenotype in ovarian carcinomas. Clin Cancer Res 11: 3225-3232, 2005.
46. Nakamura Y, Yasuoka H, Tsujimoto M, et al: Flt-4-positive vessel density correlates with vascular endothelial growth factor-D expression, nodal status, and prognosis in breast cancer. Clin Cancer Res 9: 5313-5317, 2003.
47. Jacquemier J, Mathoulin-Portier MP, Valtola R, et al: Prognosis of breast-carcinoma lymphangiogenesis evaluated by immunohistochemical investigation of vascular-endothelial-growthfactor receptor 3. Int J Cancer 89: 69-73, 2000.
48. Franchi A, Gallo O, Massi D, Baroni G and Santucci M: Tumor lymphangiogenesis in head and neck squamous cell carcinoma: a morphometric study with clinical correlations. Cancer 101: 973-978, 2004.
49. Beasley NJ, Prevo R, Banerji S, et al: Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res 62: 1315-1320, 2002.
50. Hall FT, Freeman JL, Asa SL, Jackson DG and Beasley NJ: Intratumoral lymphatics and lymph node metastases in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 129: 716-719, 2003.
51. Kitadai Y, Kodama M, Cho S, et al: Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodes. Int J Cancer 115: 388-392, 2005.
52. Thiele W and Sleeman JP: Tumor-induced lymphangiogenesis: a target for cancer therapy? J Biotechnol 124: 224-241, 2006.
53. Kurebayashi J, Otsuki T, Kunisue H, et al: Expression of vascular endothelial growth factor (VEGF) family members in breast cancer. Jpn J Cancer Res 90: 977-981, 1999.
54. Nakamura Y, Yasuoka H, Tsujimoto M, et al: Clinicopathological significance of vascular endothelial growth factor-C in breast carcinoma with long-term follow-up. Mod Pathol 16: 309-314, 2003.
55. Mohammed RA, Green A, El-Shikh S, Paish EC, Ellis IO and Martin SG: 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: 1092-1100, 2007.
56. Bando H, Weich HA, Horiguchi S, Funata N, Ogawa T and Toi M: The association between vascular endothelial growth factor-C, its corresponding receptor, VEGFR-3, and prognosis in primary breast cancer: a study with 193 cases. Oncol Rep 15: 653-659, 2006.
57. Kinoshita J, Kitamura K, Kabashima A, Saeki H, Tanaka S and Sugimachi K: Clinical significance of vascular endothelial growth factor-C (VEGF-C) in breast cancer. Breast Cancer Res Treat 66: 159-164, 2001.
58. Watanabe O, Kinoshita J, Shimizu T, et al: Expression of a CD44 variant and VEGF-C and the implications for lymphatic metastasis and long-term prognosis of human breast cancer. J Exp Clin Cancer Res 24: 75-82, 2005.
59. Okada K, Osaki M, Araki K, Ishiguro K, Ito H and Ohgi S: Expression of hypoxia-inducible factor (HIF-1alpha), VEGF-C and VEGF-D in non-invasive and invasive breast ductal carcinomas. Anticancer Res 25: 3003-3009, 2005.
60. Gunningham SP, Currie MJ, Han C, 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 6: 4278-4286, 2000.
61. Koyama Y, Kaneko K, Akazawa K, Kanbayashi C, Kanda T and Hatakeyama K: Vascular endothelial growth factor-C and vascular endothelial growth factor-D messenger RNA expression in breast cancer: association with lymph node metastasis. Clin Breast Cancer 4: 354-360, 2003.
62. Hoar FJ, Chaudhri S, Wadley MS and Stonelake PS: Coexpression of vascular endothelial growth factor C (VEGF-C) and c-erbB2 in human breast carcinoma. Eur J Cancer 39: 1698-1703, 2003.
63. Mylona E, Alexandrou P, Mpakali A, et al: Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and -D and VEGF receptor 3 in invasive breast carcinoma. Eur J Surg Oncol 33: 294-300, 2007.
64. Nagy JA, Vasile E, Feng D, et al: Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med 196: 1497-1506, 2002.
65. Hirakawa S, Kodama S, Kunstfeld R, Kajiya K, Brown LF and Detmar M: VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J Exp Med 201: 1089-1099, 2005.
66. Cao Y, Linden P, Farnebo J, et al: Vascular endothelial growth factor C induces angiogenesis in vivo. Proc Natl Acad Sci USA 95: 14389-14394, 1998.
67. Miyata Y, Kanda S, Ohba K, et al: Lymphangiogenesis and angiogenesis in bladder cancer: prognostic implications and regulation by vascular endothelial growth factors-A, -C and -D. Clin Cancer Res 12: 800-806, 2006.
68. Ogawa E, Takenaka K, Yanagihara K, et al: Clinical significance of VEGF-C status in tumour cells and stromal macrophages in non-small cell lung cancer patients. Br J Cancer 91: 498-503, 2004.
69. Saad RS, Kordunsky L, Liu YL, Denning KL, Kandil HA and Silverman JF: Lymphatic microvessel density as prognostic marker in colorectal cancer. Mod Pathol 19: 1317-1323, 2006.
70. Choi WW, Lewis MM, Lawson D, et al: Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol 18: 143-152, 2005.
71. Forsythe JA, Jiang B, Iyer N, et al: Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16: 4604-4613, 1996.
72. Maxwell PH, Dachs GU, Gleadle JM, et al: Hypoxia-inducible facrot-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA 94: 8104-8109, 1997.
73. Schoppmann SF, Fenzl A, Schindl M, et al: Hypoxia inducible factor 1α correlates with VEGF-C expression and lymphangiogenesis in breast cancer. Breast Cancer Res Treat 99: 135-141, 2006.
74. Liang X, Yang D, Hu J, Hao X Gao J and Mao Z: Hypoxia inducible facrot-1alpha expression correlates with vascular endothelial growth factor-C expression and lymphangiogenesis/ angiogenesis in oral squamous cell carcinoma. Anticancer Res 28: 1659-1666, 2008.