Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 May;84(10):1354–1362. doi: 10.1054/bjoc.2001.1809

3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon

M A Konerding 1, E Fait 1, A Gaumann 1,2
PMCID: PMC2363651  PMID: 11355947

Abstract

Despite the significance of tumour neoangiogenesis and the extensive knowledge on the molecular basis of blood vessel formation currently no quantitative data exist on the 3D microvascular architecture in human primary tumours and their precursor lesions. This prompted us to examine the 3D vascular network of normal colon mucosa, adenomas and invasive carcinomas by means of quantitative microvascular corrosion casting. Fresh hemicolectomy specimens from 20 patients undergoing cancer or polyposis coli surgery were used for corrosion casting, factor VIII and VEGF immunostaining. In addition, immunostaining was done on colorectal tissue from 33 patients with metastatic and non-metastatic carcinomas, polyposis coli and adenomas. This first quantitative analysis of intervessel and interbranching distances, branching angles and vessel diameters in human cancer specimens revealed distinct patterns of the microvascular unit in the tumour centre and periphery. Irrespective of the tumour localization and grading all individual tumours displayed qualitatively and quantitatively the same vascular architecture. This gives further evidence for the existence of a tumour type-specific vascular architecture as recently demonstrated for experimental tumours. Metastatic tumours displayed different vascular architectures only within hot spots, in terms of smaller intervascular distances than in non-metastatic tumours. Pre-cancerous lesions have in part virtually the same vascular architecture like invasive carcinomas. Comparison of VEGF immunostaining also suggests that angiogenesis sets in long before the progress towards invasive phenotypes and that the so-called angiogenic switch is more likely a sequence of events. © 2001 Cancer Research Campaign www.bjcancer.com

Keywords: angiogenesis, tumour vascular architecture, colorectal adenocarcinoma, adenoma, pre-cancerous lesions

Full Text

The Full Text of this article is available as a PDF (537.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ajiki T., Fujimori T., Ikehara H., Saitoh Y., Maeda S. K-ras gene mutation related to histological atypias in human colorectal adenomas. Biotech Histochem. 1995 Mar;70(2):90–94. doi: 10.3109/10520299509108323. [DOI] [PubMed] [Google Scholar]
  2. Arbiser J. L., Moses M. A., Fernandez C. A., Ghiso N., Cao Y., Klauber N., Frank D., Brownlee M., Flynn E., Parangi S. Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):861–866. doi: 10.1073/pnas.94.3.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med. 2000 Apr;6(4):389–395. doi: 10.1038/74651. [DOI] [PubMed] [Google Scholar]
  4. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
  5. Folkman J., D'Amore P. A. Blood vessel formation: what is its molecular basis? Cell. 1996 Dec 27;87(7):1153–1155. doi: 10.1016/s0092-8674(00)81810-3. [DOI] [PubMed] [Google Scholar]
  6. Folkman J. The vascularization of tumors. Sci Am. 1976 May;234(5):58-64, 70-3. doi: 10.1038/scientificamerican0576-58. [DOI] [PubMed] [Google Scholar]
  7. Folkman J., Watson K., Ingber D., Hanahan D. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature. 1989 May 4;339(6219):58–61. doi: 10.1038/339058a0. [DOI] [PubMed] [Google Scholar]
  8. Herlyn M., Clark W. H., Rodeck U., Mancianti M. L., Jambrosic J., Koprowski H. Biology of tumor progression in human melanocytes. Lab Invest. 1987 May;56(5):461–474. [PubMed] [Google Scholar]
  9. Ishikawa H., Fujii H., Yamamoto K., Morita T., Hata M., Koyama F., Terauchi S., Sugimori S., Kobayashi T., Enomoto H. Tumor angiogenesis predicts recurrence with normal serum carcinoembryonic antigen in advanced rectal carcinoma patients. Surg Today. 1999;29(10):983–991. doi: 10.1007/s005950050633. [DOI] [PubMed] [Google Scholar]
  10. Jain R. K. Determinants of tumor blood flow: a review. Cancer Res. 1988 May 15;48(10):2641–2658. [PubMed] [Google Scholar]
  11. Jakob W., Jentzsch K. D., Mauersberger B., Oehme P. Demonstration of angiogenesis-activity in the corpus luteum of cattle. Exp Pathol (Jena) 1977;13(4-5):231–236. doi: 10.1016/s0014-4908(77)80007-0. [DOI] [PubMed] [Google Scholar]
  12. Kitadai Y., Haruma K., Tokutomi T., Tanaka S., Sumii K., Carvalho M., Kuwabara M., Yoshida K., Hirai T., Kajiyama G. Significance of vessel count and vascular endothelial growth factor in human esophageal carcinomas. Clin Cancer Res. 1998 Sep;4(9):2195–2200. [PubMed] [Google Scholar]
  13. Konerding M. A., Fait E., Dimitropoulou C., Malkusch W., Ferri C., Giavazzi R., Coltrini D., Presta M. Impact of fibroblast growth factor-2 on tumor microvascular architecture. A tridimensional morphometric study. Am J Pathol. 1998 Jun;152(6):1607–1616. [PMC free article] [PubMed] [Google Scholar]
  14. Konerding M. A., Malkusch W., Klapthor B., van Ackern C., Fait E., Hill S. A., Parkins C., Chaplin D. J., Presta M., Denekamp J. Evidence for characteristic vascular patterns in solid tumours: quantitative studies using corrosion casts. Br J Cancer. 1999 May;80(5-6):724–732. doi: 10.1038/sj.bjc.6690416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Konerding M. A., Miodonski A. J., Lametschwandtner A. Microvascular corrosion casting in the study of tumor vascularity: a review. Scanning Microsc. 1995;9(4):1233–1244. [PubMed] [Google Scholar]
  16. Malkusch W., Konerding M. A., Klapthor B., Bruch J. A simple and accurate method for 3-D measurements in microcorrosion casts illustrated with tumour vascularization. Anal Cell Pathol. 1995 Jul;9(1):69–81. [PubMed] [Google Scholar]
  17. Millauer B., Shawver L. K., Plate K. H., Risau W., Ullrich A. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature. 1994 Feb 10;367(6463):576–579. doi: 10.1038/367576a0. [DOI] [PubMed] [Google Scholar]
  18. Okada F., Rak J. W., Croix B. S., Lieubeau B., Kaya M., Roncari L., Shirasawa S., Sasazuki T., Kerbel R. S. Impact of oncogenes in tumor angiogenesis: mutant K-ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cells. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3609–3614. doi: 10.1073/pnas.95.7.3609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Smith-McCune K. K., Weidner N. Demonstration and characterization of the angiogenic properties of cervical dysplasia. Cancer Res. 1994 Feb 1;54(3):800–804. [PubMed] [Google Scholar]
  20. Takahashi Y., Bucana C. D., Cleary K. R., Ellis L. M. p53, vessel count, and vascular endothelial growth factor expression in human colon cancer. Int J Cancer. 1998 Feb 20;79(1):34–38. doi: 10.1002/(sici)1097-0215(19980220)79:1<34::aid-ijc7>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  21. Takahashi Y., Tucker S. L., Kitadai Y., Koura A. N., Bucana C. D., Cleary K. R., Ellis L. M. Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer. Arch Surg. 1997 May;132(5):541–546. doi: 10.1001/archsurg.1997.01430290087018. [DOI] [PubMed] [Google Scholar]
  22. Weidner N., Carroll P. R., Flax J., Blumenfeld W., Folkman J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol. 1993 Aug;143(2):401–409. [PMC free article] [PubMed] [Google Scholar]
  23. Weidner N., Folkman J., Pozza F., Bevilacqua P., Allred E. N., Moore D. H., Meli S., Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992 Dec 16;84(24):1875–1887. doi: 10.1093/jnci/84.24.1875. [DOI] [PubMed] [Google Scholar]
  24. Weidner N., Semple J. P., Welch W. R., Folkman J. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med. 1991 Jan 3;324(1):1–8. doi: 10.1056/NEJM199101033240101. [DOI] [PubMed] [Google Scholar]
  25. Wong M. P., Cheung N., Yuen S. T., Leung S. Y., Chung L. P. Vascular endothelial growth factor is up-regulated in the early pre-malignant stage of colorectal tumour progression. Int J Cancer. 1999 Jun 11;81(6):845–850. doi: 10.1002/(sici)1097-0215(19990611)81:6<845::aid-ijc1>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  26. Yancopoulos G. D., Klagsbrun M., Folkman J. Vasculogenesis, angiogenesis, and growth factors: ephrins enter the fray at the border. Cell. 1998 May 29;93(5):661–664. doi: 10.1016/s0092-8674(00)81426-9. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES