Abstract
The sprouting of new blood vessels from pre-existing vasculature (angiogenesis) is essential for tumour survival, influenced by tumour cell-endothelial cell interactions and is tightly regulated by biochemical cues including the kallikrein-kinin system (KKS). We examined the structural interaction between neuroblastomas and endothelial cells (HUVECs) in 2-D and 3-D (matrigel) in vitro, co-culture models by light microscopy, and performed in situ mono- and co-labelling of various KKS proteins. Neuroblastomas formed footplate-like multiple contacts on angiogenic HUVECs without disrupting differentiation of HUVECs into cord-like structures. Tissue kallikrein and the kinin B1R and B2R receptors were demonstrated on interacting neuroblastomas and HUVECs to varying degrees, as well as at actual heterogeneous contact zones in both 2-D and 3-D models. This KKS immuno-reactivity was generally confined to peri-nuclear regions on HUVECs but concentrated on cell extensions on neuroblastomas. The KKS, known to enhance DNA synthesis and process pro-angiogenic precursors of both tumour cells and the extra-cellular matrix, may, by its multi-functional activities at sites of tumour-blood vessel interactions, regulate aspects of both angiogenesis and tumourigenesis.
Similar content being viewed by others
References
Bhoola KD, Elson CJ, Dieppe PA (1992a) Kinins-key mediators ininflammatory arthritis. Br J Rheum 31:509–518
Bhoola KD, Figueroa CD, Worthy K (1992b) Bioregulation of Kinins: Kallikreins, kininogens and kininases. Pharmacol Rev 44:1–80
Bischoff J (1997) Cell adhesion and angiogenesis. J Clin Invest 99:373–376
Borgono C, Micheal I, Diamandis E (2004) Human tissue kallikreins: Physiologic roles and applications in cancer. Mol Cancer Res 2:257–280
Chen L-M, Song Q, Chao L, Chao J (1995) Cellular localisation oftissue kallikrein and kallistatin mRNAs in human kidney. Kid Int 48:690–697
Dedio J, Wiemer G, Rutten H, Dendorfer A, Scholkens B, Muller-Esterl W, Wohlfart P (2001) Tissue kallikrein KLK1 is expressed de novo inendothelial cells and mediates relaxation of human umbilical veins. J Biol Chem 382:1483–1490
Desrivieres S, Lu H, Peyri N, Soria C, Legrand Y, Menashi S (1993) Activation of the 92 kDa type IV collagenase by tissue kallikrein. J Cell Physiol 157:587–593
Diamandis EP, Yousef GM (2002) Human tissue kallikreins: A family of new cancer biomarkers. Clin Chem 48:1198–1205
Diamandis EP, Yousef GM, Luo L-Y, Magklara A, Obiezu CV (2000) The new human kallikrein gene family: Implications in carcinogenesis. Trends Endocrinol Metab 11:54–60
Emanueli C, Minasi A, Zacheo A, Chao J, Chao L, Salis M, Straino S, Tozzi M, Smith R, Gaspa L, Bianchini G, Stillo F, Capogrossi M, Madeddu P (2001a) Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia. Circulation 103:125–132
Emanueli C, Salis M, Stacca T, Pintus G, Kirchmair R, Isner J, Pinna A, Gaspa L, Regoli D, Cayla C, Pesquero J, Bader M, Madeddu P (2001b) Targeting kinin B1 receptor for therapeutic neovascularization. Circulation 105:360–366
Emanueli C, Schratzberger P, Kirchmair R, Madeddu P (2003) Paracrine control of vascularization and neurogenesis by neurotrophins. Br J Pharmacol 140:614–619
Ferrara N (1996) Vascular endothelium growth factor. Eur J Cancer 32A:2413–2422
Ferrara N, Alitalo K (1999) Clinical applications for angiogenic growth factors and their inhibitors. Nat Med 5:1359–1364
Ferrer FA, Miller LJ, Andrawis RI, Kurtzman SH, Albertsen PC, Laudone VP, Kreutzer DL (1997) Vascular endothelial growth factor (VEGF) expression in human prostate cancer: In situ and in vitro expression of VEGF by human prostate cancer cells. J Urol 157:2329–2333
Folberg R, Hendrix MJC, Maniotis AJ (2000) Vasculogenic mimicryand tumor angiogenesis. Am J Pathol 156:361–381
Folkman J (1971) Tumour angiogenesis: Therapeutic implications. N Engl J Med 285:1182–1186
Folkman J (1972) Anti-angiogenesis: New concept for therapy of solid tumors. Ann Surg 175:409–416
Folkman J (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29:15–18
Folkman J, Haudenschild C (1980) Angiogenesis in vitro. Nature 288:551–556
Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934
Gargett CE, Bucak K, Rogers PAW (2000) Isolation, characterization and long-term culture of human myometrial microvascular endothelial cells. Hum Reprod 15:293–301
Graf K, Grafe M, Auch-Schwelk W, Baumgarten CR, Scheffer H, Hildebrandt AEF (1994) Tissue kallikrein activity and kinin release in human endothelial cells. Eur J Clin Chem Clin Biochem 32:495–500
Griffioen AW, Barendz-Janson AF, Mayo KH, Hillen HFP (1998) Angiogenesis, a target for tumor therapy. J Lab Clin Med 132:363–368
Ishihara K, Hayash I, Yamashina SMM (2001) A potential role of bradykinin in angiogenesis and growth of S-180 mouse tumors. Jpn J Pharmacol 87:4
Jackson C, Nguyen M, Arkell J, Sambrook P (2001) Selective matrixmetalloproteinase (MMP) inhibition in rheumatoid arthritis-targetting gelatinase A activation. Inflam Res 50:183–186
Kataoka H, Itoh H, Koono M (2002) Emerging multifunctional aspects of cellular serine proteinase inhibitors in tumor progression and tissue regeneration. Pathol Int 52:89–102
Kisker O, Onizuka S, Becker C, Fannon M, Flynn E, D’Amato R, Zetter B, Folkman J, Ray R, Swamy N, Pirie-Shephard S (2003) Vitamin D binding protein-macrophage activating factor (DBF-maf) inhibits angiogenesis and tumor growth. Neoplasia 5:32–40
Koch A (1998) Angiogenesis: Implications for rheumatoid arthritis. Arthritis Rheum 41:951–962
Mason D, Sammons R (1978) Alkaline phosphatase and peroxidase for double immunoenzymatic labbeling of cellular constituents. J Clin Pathol 31:454–460
Matsumura Y, Kimura M, Yamamoto T, Konno T, Maeda H (1988) Involvement of the kinin generating cascade in enhanced vascular permeability intumour tissue. Jpn J Cancer Res 79:1327–1334
Naidoo S, Raidoo D, Mahabeer R, McLean M (2004) Tumour metabolites regulate tissue kallikrein in human umbilical vein endothelial cells. Biochim Biophys Acta 1691:117–127
Naidoo S, Ramsaroop R, Bhoola R, Bhoola K (1997) The evaluation of tissue kallikrein in Helicobacter pylori-associated gastric ulcer disease. Immunopharm 36:263–269
Naidoo S, Ramsaroop R, Bhoola R, Bhoola K (1999) Correlation ofkinin-generating activity with Helicobacter pylori-associated gastric infection. Immunopharm 43:225–233
Naidoo S, Ramsaroop R, Naidoo Y, Bhoola KD (1996) The status of B2 receptors in acute renal transplant rejection. Immunopharm 33:157–160
Naidoo V, Naidoo S, Mahabeer R, Raidoo D (2005) Localization of the endothelin system in human diffuse astrocytomas. Cancer 104:1049–1057
Nolly H, Nolly A (1988) Release of endothelial-derived kallikrein, kininogen and kinins. Biol Res 31:169–174
Plendl J, Snyman C, Naidoo S, Sawant S, Mahabeer R, Bhoola KD (2000) Expression of tissue kallikrein and kinin receptors in angiogenic microvascular endothelial cells. J Biol Chem 281:1103–1115
Raidoo D, Sawant S, Mahabeer RKDB (1999) Kinin receptors are expressed in human astrocytic tumour cells. Immunopharm 43:255–263
Raidoo DM, Ramchurren N, Naidoo Y, Naidoo S, Müller-Esterl W, Bhoola KD (1996a) Visualisation of bradykinin B2 receptors on human brain neurons. Immunopharm 33:104–107
Raidoo DM, Ramsaroop R, Naidoo S, Bhoola KD (1996b) Regional distribution of tissue kallikrein in the human brain. Immunopharm 32:39–47
Raidoo DM, Ramsaroop R, Naidoo S, Bhoola KD (1997) Visualisation of tissue kallikrein and kinin receptors in human astrocytomas. Br J Pharmacol 122:107
Rixon RH, Whitfield JF (1973) Kininogenases, kallikrein. Schattauer-Verlag. Stuttgart.
Sambrook J, Fritsch E, Maniatis T (1989) Molecular Cloning. A Laboratory Manual. Cold Spring Harbour Press. New York
Seyedi N, Xu Z, Nasjletti A, Hintze T (1995) Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation. Hypertension 26:164–170
Silvestre J-S, Bergaya S, Tamarat RMD, Boulanger C, Levy B (2001) Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by the bradykinin B2 receptor pathway. Circ Res 89:678–683
Tscheche H, Michealis J, Kohnert U, Fedrowitz J, Oberhoff R (1989) Tissue kallikrein effectively activates latent matrix degrading metalloenzymes. Adv Exp Med Biol 247A:545–548
Wu J, Akaide T, Maeda H (1998) Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclo-oxygenase inhibitor, and a nitrogen oxide scavenger. Cancer Res 58:159–165
Wu J, Akaike T, Hayashida K, Miyamoto Y, Nakagawa T, Miyakawa K, Muller Esterl W, Maeda H (2002) Identification of bradykinin receptors in clinical cancer specimens and murine tumor tissues. Int J Cancer 98:29–35
Yayama K, Kunimatsu N, Teranishi Y, Takano M, Okamoto H (2003) Tissue kallikrein is synthesized and secreted by human vascular endothelial cells. Biochim Biophys Acta 1593:231–238
Yousef G, Diamandis E (2001) The new human tissue kallikrein gene family: Structure, function and association to disease. Endocr Rev 22:184–202
Yu J, Rak J, Coomber B, Hicklin D, Kerbel R (2002) Effect of p53 status on tumor response to antiangiogenic therapy. Science 295:1526–1528
Acknowledgments
The authors thank the National Research Foundation (NRF) of South Africa for financial support, as well as the Research Office, University of KwaZulu Natal.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Naidoo, S., Raidoo, D.M. Tissue kallikrein and kinin receptor expression in an angiogenic co-culture neuroblastoma model. Metab Brain Dis 21, 242–254 (2006). https://doi.org/10.1007/s11011-006-9008-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-006-9008-3