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Table of Contents
Vol. 78, No. 1, 2011
Issue release date: April 2011
Section title: Original Paper
Pathobiology 2011;78:24–34

Vascular Pericyte Density and Angiogenesis Associated with Adenocarcinoma of the Prostate

Killingsworth M.C.a–c · Wu X.a, c
aDepartment of Anatomical Pathology, South Western Area Pathology Service, bFaculty of Medicine, University of New South Wales, and cSchool of Medicine, University of Western Sydney, Sydney, N.S.W., Australia
email Corresponding Author

Assoc. Prof. Murray Killingsworth, PhD

Department of Anatomical Pathology

South Western Area Pathology Service, Locked Bag 7090

Sydney, NSW 1871 (Australia)

Tel. +61 2 9828 5392, Fax +61 2 9828 5328, E-Mail m.killingsworth@unsw.edu.au


  1. Bergers G, Song S: The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 2005;7:452–464.
  2. Adams RH, Alitalo K: Molendothelial cellular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 2007;8:464–478.
  3. Brawer MK, Deering RE, Brown M, Preston SD, Bigler SA: Predictors of pathologic stage in prostatic carcinoma: the role of neovascularity. Cancer 1994;73:678–687.
  4. Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J: Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 1993;143:401–409.
  5. Pallares J, Rojo F, Iriarte J, Morote J, Armadans LI, de Torres I: Study of microvessel density and the expression of the angiogenic factors VEGF, bFGF and the receptors Flt-1 and FLK-1 in benign, premalignant and malignant prostate tissues. Histol Histopathol 2006;21:857–865.
  6. Weidner N: Editorial: Tumoral vascularity as a prognostic factor in cancer patients: the evidence continues to grow. J Pathol 1998;184:119–122.
  7. Concato J, Jain D, Uchio E, Risch H, Li WW, Wells CK: Molecular markers and death from prostate cancer. Ann Intern Med 2009;150:595–603.
  8. Chodak GW, Warren KS: Watchful waiting for prostate cancer: a review article. Prostate Cancer Prostatic Dis 2006;9:25–29.
  9. De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG: Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007;7:256–269.
  10. Sivridis E, Giatromanolaki A, Koukourakis MI: The vascular network of tumors – what is it not for? J Pathol 2003;201:173–180.
  11. Wang Y, Wan C, Deng L, Liu X, Cao X, Gilbert SR, Bouxsein ML, Faugere M, Guldberg RE, Gerstenfeld LC, Haase VH, Johnson RS, Schipani E, Clemens TL: The hypoxia-inducible factor α pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest 2007;117:1616–1626.
  12. Tozer GM, Lewis S, Michalowski A, Aber V: The relationship between regional variations in blood flow and histology in a transplanted rat fibrosarcoma. Br J Cancer 1990;61:250–257.
  13. Allsbrook WC Jr, Simms WW: Histochemistry of the prostate. Hum Pathol 1992;23:297–305.
  14. Weidner N, Semple JP, Wech WR, Folkman J: Tumor angiogenesis and metastasis – correlation in invasive breast carcinoma. N Engl J Med 1991;324:1–8.
  15. Borre M, Offersen BV, Nerstrom B, Overgaard J: Microvessel density predicts survival in prostate cancer patients subjected to watchful waiting. Br J Cancer 1998;78:940–944.
  16. Wakui S, Furusato M, Itoh T, Sasaki H, Akiyama A, Kinoshita I, Asano K, Tokuda T, Aizawa S, Ushigome S: Rapid communication: tumor angiogenesis in prostatic carcinoma with and without bone marrow metastasis: a morphometric study. J Pathol 1992;168:257–262.
  17. Sharma S, Sharma MC, Sarkar C: Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis. Histopathology 2005:46:481–489.
  18. American Joint Committee on Cancer: Prostate; in Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M (eds): AJCC Cancer Staging Manual, ed 6. Berlin, Springer, 2002, pp 309–313.
  19. Jain RK: Molecular regulation of vessel maturation. Nat Med 2003;9:685–693.
  20. Ausprunk DH, Folkman J: Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 1977;14:53–65.
  21. Nehls V, Denzer K, Drenckhahn D: Pericyte involvement in capillary sprouting during angiogenesis in situ. Cell Tissue Res 1992;270:469–474.
  22. Killingsworth MC: Angiogenesis in early choroidal neovascularization secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 1995;233:313–323.
  23. Ozerdem U, Stallcup WB: Early contribution of pericytes to angiogenic sprouting and tube formation. Angiogenesis 2003;6:241–249.
  24. Reynolds LP, Grazul-Bilska AT, Redmer DA: Angiogenesis in the corpus luteum. Endocrine 2000;12:1–9.
  25. Stratman AN, Malotte KM, Mahan RD, Davis MJ, Davis GE: Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. Blood 2009;114:5091–5101.
  26. Chen CW, Montelatici E, Crisan M, Corselli M, Huard J, Lazzari L, Peault B: Perivascular multi-lineage progenitor cells in human organs: regenerative units, cytokine sources or both? Cytokine Growth Factor Rev 2009;20:429–434.
  27. Crisan M, Chen CW, Corselli M, Andriolo G, Lazzari L, Peault B: Perivascular mulipotent progenitor cells in human organs. Ann NY Acad Sci 2009;1176:118–123.
  28. Diaz-Flores L, Gutierrez R, Madrid JF, Varela H, Valladares F, Acosta E, Martin-Vassallo P, Diaz-Flores L Jr: Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. Histol Histopathol 2009;24:909–969.
  29. Ozerdem U, Grako KA, Dahlin-Huppe K, Monosov E, Stallcup WB: NG2 proteoglycan is expressed by mural cells during vascular morphogenesis. Dev Dyn 2001;222:218–227.
  30. Verbeek MM, Otte-Holler I, Wesseling P, Ruiter DJ, de Waal RMW: Induction of α-smooth muscle actin expression in cultured human brain pericytes by transforming growth factor-β1. Am J Pathol 1994;144:372–382.
  31. Song S, Ewald AJ, Stallcup W, Werb Z, Bergers G: PDGFRβ+ perivascular progenitor cells in tumors regulate pericyte differentiation and vascular survival. Nat Cell Biol 2005;7:870–879.
  32. Song N, Huang Y, Shi H, Yuan S, Ding Y, Song X, Fu Y, Luo Y: Overexpression of platelet-derived growth factor-BB increases tumor pericyte content via stromal-derived factor-1αCXCR4 axis. Cancer Res 2009;69:6057–6064.
  33. Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D: Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 2003;111:1287–1295.
  34. Greenberg JI, Cheresh DA: VEGF as an inhibitor of tumor vessel maturation: implications for cancer therapy. Expert Opin Biol Ther 2009;9:1347–1356.
  35. Helfrich I, Scheffrahn I, Bartling S, Weis J, von Felbert V, Middleton M, Kato M, Ergun S, Schadendorf D: Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma. J Exp Med 2010;207:491–503.
  36. Hellberg C, Ostman A, Heldin CH: PDGF and vessel maturation. Recent Results Cancer Res 2010;180:103–114.
  37. Ozerdem U: Targeting of pericytes diminishes neovascularization and lymphangiogenesis in prostate cancer. Prostate 2006;66:294–304.
  38. Livanainen E, Lauttia S, Zhang N, Tvorogov D, Kulmala J, Grenman R, Salven P, Elenius K: The EGFR inhibitor gefitinib suppresses recruitment of pericytes and bone marrow-derived perivascular cells into tumor vessels. Microvasc Res 2009;78:278–285.
  39. Vartanian RK, Weidner N: Endothelial cell proliferation in prostatic carcinoma and prostatic hyperplasia: correlation with Gleason’s score, microvessel density and epithelial cell proliferation. Lab Invest 1995;73:844–850.
  40. Seigal JA, Brawer MK: Topography of neovascularity in human prostate carcinoma. Cancer 1995;75:2545–2551.
  41. Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86:353–364.
  42. Bergers G, Benjamin LE: Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003;3:401–410.
  43. Soares AB, Juliano PB, Araujo VC, Metze K, Altemani A: Angiogenic switch during tumor progression of carcinoma ex-pleomorphic adenoma. Virchows Arch 2007;451:65–71.
  44. Morikawa S, Baluk P, Kaidoh T, Haskell A, Jain RK, McDonald DM: Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol 2002;160:985–1000.
  45. Gerhardt H, Betsholtz C: Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 2003;314:15–23.
  46. Guillemin GJ, Brew BJ: Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J Leukocyte Biol 2004;75:388–397.
  47. Kruger M, Bechmann I: CNS pericytes: concepts, misconceptions, and a way out. Glia 2010;58:1–10.
  48. Schlingemann RO, Rietveld FJR, de Waal RMW, Ferrone S, Ruiter DJ: Expression of the high molendothelial cellular weight melanoma-associated antigen by pericytes during angiogenesis in tumors and in healing wounds. Am J Pathol 1990;136:1393–1405.
  49. Orlidge A, D’Amore PA: Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. J Cell Biol 1987;105:1455–1462.