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Non-random spatial relationships between mast cells and microvessels in human endometrial carcinoma

Clinical and Experimental Medicine volume 17, pages 71–77 (2017)Cite this article

Abstract

Mast cells (MCs) accumulate in the stroma surrounding tumors, where they secrete angiogenic cytokines and proteases, and an increased number of MCs have been demonstrated in angiogenesis associated with solid and hematological tumors. The aim of this study is to contribute to the knowledge of distribution of MCs in tumors, investigating the pattern of distribution of tryptase-positive MCs around the blood vessels in human endometrial carcinoma samples by introducing a quantitative approach to characterize their spatial distribution. The results have shown that in human endometrial cancer bioptic specimens the spatial distribution of MCs shows significant deviation from randomness as compared with control group in which, instead, the spatial distribution of MCs is consistent with a random distribution. These findings confirm that MCs enhance tumor angiogenesis and their preferential localization along blood vessels and sites of new vessel formation sustaining the suggestion for an association between MCs and angiogenesis. However, this spatial association between vessels and MCs might simply reflect migrating MCs from the blood stream at vessel growing sites.

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References

  1. Ribatti D, Finato N, Crivellato E, Marzullo A, Mangieri D, Nico B, et al. Neovascularization and mast cells with tryptase activity increase simultaneously with pathologic progression in human endometrial cancer. Am J Obstet Gynecol. 2005;193(6):1961–5. doi:10.1016/j.ajog.2005.04.055.

    CAS  Article  PubMed  Google Scholar 

  2. Ribatti D, Nico B, Finato N, Crivellato E. Tryptase-positive mast cells and CD8-positive T cells in human endometrial cancer. Pathol Int. 2011;61(7):442–4. doi:10.1111/j.1440-1827.2011.02680.x.

    Article  PubMed  Google Scholar 

  3. Guidolin D, Nico B, Crivellato E, Marzullo A, Vacca A, Ribatti D. Tumoral mast cells exhibit a common spatial distribution. Cancer Lett. 2009;273(1):80–5. doi:10.1016/j.canlet.2008.07.032.

    CAS  Article  PubMed  Google Scholar 

  4. Ruifrok AC, Katz RL, Johnston DA. Comparison of quantification of histochemical staining by hue-saturation-intensity (HSI) transformation and color-deconvolution. Appl Immunohistochem Mol Morphol. 2003;11(1):85–91. doi:10.1097/00129039-200303000-00014.

    CAS  PubMed  Google Scholar 

  5. Jc R. The image processing handbook. Boca Raton: CRC Press; 1995. p. 272.

    Google Scholar 

  6. Besag J, Diggle PJ. Simple monte carlo tests for spatial pattern. Appl Stat. 1977;26(3):327. doi:10.2307/2346974.

    Article  Google Scholar 

  7. Gatrell AC, Bailey TC, Diggle PJ, Rowlingson BS. Spatial point pattern analysis and its application in geographical epidemiology. Trans Inst Br Geogr. 1996;21(1):256. doi:10.2307/622936.

    Article  Google Scholar 

  8. Philimonenko AA, Janáček J, Hozák P. Statistical evaluation of colocalization patterns in immunogold labeling experiments. J Struct Biol. 2000;132(3):201–10. doi:10.1006/jsbi.2000.4326.

    CAS  Article  PubMed  Google Scholar 

  9. Eady RAJ, Cowen T, Marshall TF, Plummer V, Greaves MW. Mast cell population density, blood vessel density and histamine content in normal human skin. Br J Dermatol. 1979;100(6):623–33. doi:10.1111/j.1365-2133.1979.tb08065.x.

    CAS  Article  PubMed  Google Scholar 

  10. Rakusan K, Sarkar K, Turek Z, Wicker P. Mast cells in the rat heart during normal growth and in cardiac hypertrophy. Circ Res. 1990;66(2):511–6. doi:10.1161/01.res.66.2.511.

    CAS  Article  PubMed  Google Scholar 

  11. Rhodin JA, Fujita H. Capillary growth in the mesentery of normal young rats. Intravital video and electron microscope analyses. J Submicrosc Cytol Pathol. 1989;21(1):1–34.

    CAS  PubMed  Google Scholar 

  12. Trabucchi E, Radaelli E, Marazzi M, Foschi D, Musazzi M, Veronesi AM, et al. The role of mast cells in wound healing. Int J Tissue React. 1988;10(6):367–72.

    CAS  PubMed  Google Scholar 

  13. Krishna A, Beesley K, Terranova PF. Histamine, mast cells and ovarian function. J Endocrinol. 1989;120(3):363–71. doi:10.1677/joe.0.1200363.

    CAS  Article  PubMed  Google Scholar 

  14. Yamada T, Sawatsubashi M, Itoh Y, Edakuni G, Mori M, Robert L, et al. Localization of vascular endothelial growth factor in synovial membrane mast cells: examination with “multi-labelling subtraction immunostaining”. Virchows Arch. 1998;433(6):567–70. doi:10.1007/s004280050290.

    CAS  Article  PubMed  Google Scholar 

  15. Ribatti D. Mast cells and macrophages exert beneficial and detrimental effects on tumor progression and angiogenesis. Immunol Lett. 2013;152(2):83–8. doi:10.1016/j.imlet.2013.05.003.

    CAS  Article  PubMed  Google Scholar 

  16. Glowacki J, Mulliken JB. Mast cells in hemangiomas and vascular malformations. Pediatrics. 1982;70(1):48–51.

    CAS  PubMed  Google Scholar 

  17. Qu Z, Kayton RJ, Ahmadi P, Liebler JM, Powers MR, Planck SR, et al. Ultrastructural immunolocalization of basic fibroblast growth factor in mast cell secretory granules: morphological evidence for bFGF release through degranulation. J Histochem Cytochem. 1998;46(10):1119–28. doi:10.1177/002215549804601004.

    CAS  Article  PubMed  Google Scholar 

  18. Fukushima N, Satoh T, Sano M, Tokunaga O. Angiogenesis and mast cells in non-Hodgkin’s lymphoma: a strong correlation in angioimmunoblastic T-cell lymphoma. Leuk Lymphoma. 2001;42(4):709–20. doi:10.3109/10428190109099333.

    CAS  Article  PubMed  Google Scholar 

  19. Marinaccio C, Ingravallo G, Gaudio F, Perrone T, Nico B, Maoirano E, et al. Microvascular density, CD68 and tryptase expression in human diffuse large B-cell lymphoma. Leuk Res. 2014;38(11):1374–7. doi:10.1016/j.leukres.2014.09.007.

    CAS  Article  PubMed  Google Scholar 

  20. Ribatti D, Nico B, Vacca A, Marzullo A, Calvi N, Roncali L, et al. Do mast cells help to induce angiogenesis in B-cell non-Hodgkin’s lymphomas? Br J Cancer. 1998;77(11):1900–6. doi:10.1038/bjc.1998.316.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. Ribatti D, Vacca A, Marzullo A, Nico B, Ria R, Roncali L, et al. Angiogenesis and mast cell density with tryptase activity increase simultaneously with pathological progression in B-cell non-Hodgkin’s lymphomas. Int J Cancer. 2000;85(2):171–5. doi:10.1002/(sici)1097-0215(20000115)85:2<171:aid-ijc4>3.0.co;2-w.

    CAS  Article  PubMed  Google Scholar 

  22. Ribatti D, Vacca A, Nico B, Quondamatteo F, Ria R, Minischetti M, et al. Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma. Br J Cancer. 1999;79(3/4):451–5. doi:10.1038/sj.bjc.6690070.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Ribatti D, Polimeno G, Vacca A, Marzullo A, Crivellato E, Nico B, et al. Correlation of bone marrow angiogenesis and mast cells with tryptase activity in myelodysplastic syndromes. Leukemia. 2002;16(9):1680–4. doi:10.1038/sj.leu.2402586.

    CAS  Article  PubMed  Google Scholar 

  24. Molica S, Vacca A, Crivellato E, Cuneo A, Ribatti D. Tryptase-positive mast cells predict clinical outcome of patients with early B-cell chronic lymphocytic leukemia. Eur J Haematol. 2003;71(2):137–9. doi:10.1034/j.1600-0609.2003.00110.x.

    Article  PubMed  Google Scholar 

  25. Bowrey PF, King J, Magarey C, Schwartz P, Marr P, Bolton E, et al. Histamine, mast cells and tumour cell proliferation in breast cancer: does preoperative cimetidine administration have an effect? Br J Cancer. 2000;82(1):167–70. doi:10.1054/bjoc.1999.0895.

    CAS  Article  PubMed  Google Scholar 

  26. Hartveit F. Mast cells and metachromasia in human breast cancer: their occurrence, significance and consequence: a preliminary report. J Pathol. 1981;134(1):7–11. doi:10.1002/path.1711340103.

    CAS  Article  PubMed  Google Scholar 

  27. Lachter J, Stein M, Lichtig C, Eidelman S, Munichor M. Mast cells in colorectal neoplasias and premalignant disorders. Dis Colon Rectum. 1995;38(3):290–3. doi:10.1007/bf02055605.

    CAS  Article  PubMed  Google Scholar 

  28. Benitez-Bribiesca L, Wong A, Utrera D, Castellanos E. The role of mast cell tryptase in neoangiogenesis of premalignant and malignant lesions of the uterine cervix. J Histochem Cytochem. 2001;49(8):1061–2. doi:10.1177/002215540104900816.

    CAS  Article  PubMed  Google Scholar 

  29. Graham RM, Graham JB. Mast cells and cancer of the cervix. Surg Gynecol Obstet. 1966;123(1):3–9.

    CAS  PubMed  Google Scholar 

  30. Dvorak AM, Mihm MC Jr, Osage JE, Dvorak HF. Melanoma. An ultrastructural study of the host inflammatory and vascular responses. J Investig Dermatol. 1980;75(5):388–93. doi:10.1111/1523-1747.ep12523627.

    CAS  Article  PubMed  Google Scholar 

  31. Reed JA, McNutt NS, Bogdany JK, Albino AP. Expression of the mast cell growth factor interleukin-3 in melanocytic lesions correlates with an increased number of mast cells in the perilesional stroma: implications for melanoma progression. J Cutan Pathol. 1996;23(6):495–505. doi:10.1111/j.1600-0560.1996.tb01441.x.

    CAS  Article  PubMed  Google Scholar 

  32. Ribatti D, Ennas MG, Vacca A, Ferreli F, Nico B, Orru S, et al. Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma. Eur J Clin Investig. 2003;33(5):420–5. doi:10.1046/j.1365-2362.2003.01152.x.

    CAS  Article  Google Scholar 

  33. Ribatti D, Molica S, Vacca A, Nico B, Crivellato E, Roccaro AM, et al. Tryptase-positive mast cells correlate positively with bone marrow angiogenesis in B-cell chronic lymphocytic leukemia. Leukemia. 2003;17(7):1428–30. doi:10.1038/sj.leu.2402970.

    CAS  Article  PubMed  Google Scholar 

  34. Ribatti D, Vacca A, Ria R, Marzullo A, Nico B, Filotico R, et al. Neovascularisation, expression of fibroblast growth factor-2, and mast cells with tryptase activity increase simultaneously with pathological progression in human malignant melanoma. Eur J Cancer. 2003;39(5):666–74. doi:10.1016/s0959-8049(02)00150-8.

    CAS  Article  PubMed  Google Scholar 

  35. Ullah E, Nagi A, Lail R. Angiogenesis and mast cell density in invasive pulmonary adenocarcinoma. J Can Res Ther. 2012;8(4):537. doi:10.4103/0973-1482.106530.

    CAS  Article  Google Scholar 

  36. Toth-Jakatics R, Jimi S, Takebayashi S, Kawamoto N. Cutaneous malignant melanoma: correlation between neovascularization and peritumor accumulation of mast cells overexpressing vascular endothelial growth factor. Hum Pathol. 2000;31(8):955–60.

    CAS  Article  PubMed  Google Scholar 

  37. Guidolin D, Crivellato E, Nico B, Andreis P, Nussdorfer G, Ribatti D. An image analysis of the spatial distribution of perivascular mast cells in human melanoma. Int J Mol Med. 2006;. doi:10.3892/ijmm.17.6.981.

    Google Scholar 

  38. Bd R. Tests for randomness for spatial point patterns. J R Stat Soc. 1979;B41:368–74.

    Google Scholar 

  39. Pj D. Statistical analysis of spatial point patterns. London: Academic Press; 1983. p. 354.

    Google Scholar 

  40. Meininger CJ. Mast cells and tumor-associated angiogenesis. Chem Immunol. 1995;62:239–57.

    CAS  Article  PubMed  Google Scholar 

  41. Mierke CT, Ballmaier M, Manns MP, Welte K, Bischoff SC. Endothelial cells support survival of human intestinal mast cells by a direct cell-cell interaction. Gastroenterology. 2000;118(4):A360–1. doi:10.1016/s0016-5085(00)83547-7.

    Article  Google Scholar 

  42. Silverman AJ, Sutherland AK, Wilhelm M, Silver R. Mast cells migrate from blood to brain. J Neurosci. 2000;20(1):401–8.

    CAS  PubMed  Google Scholar 

  43. Watanabe Y, Lee SW, Detmar M, Ajioka I, Dvorak HF. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) delays and induces escape from senescence in human dermal microvascular endothelial cells. Oncogene. 1997;14(17):2025–32. doi:10.1038/sj.onc.1201033.

    CAS  Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported in part by a grant from “Associazione Italiana Mastocitosi.”

Author information

Affiliations

  1. Department of Molecular Medicine, University of Padova Medical School, Padua, Italy

    Diego Guidolin & Cinzia Tortorella

  2. Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, Piazza Giulio Cesare, 11, 70124, Bari, Italy

    Christian Marinaccio, Tiziana Annese, Simona Ruggieri & Domenico Ribatti

  3. Department of Biological and Medical Sciences, University of Udine Medical School, Udine, Italy

    Nicoletta Finato

  4. Department of Experimental and Clinical Medical Sciences, University of Udine Medical School, Udine, Italy

    Enrico Crivellato

  5. National Cancer Institute “Giovanni Paolo II”, Bari, Italy

    Domenico Ribatti

Authors
  1. Diego Guidolin
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  2. Christian Marinaccio
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  3. Cinzia Tortorella
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  4. Tiziana Annese
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  5. Simona Ruggieri
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  6. Nicoletta Finato
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  7. Enrico Crivellato
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  8. Domenico Ribatti
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Correspondence to Domenico Ribatti.

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Guidolin, D., Marinaccio, C., Tortorella, C. et al. Non-random spatial relationships between mast cells and microvessels in human endometrial carcinoma. Clin Exp Med 17, 71–77 (2017). https://doi.org/10.1007/s10238-016-0407-4

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  • DOI: https://doi.org/10.1007/s10238-016-0407-4

Keywords

  • Endometrial carcinoma
  • Mast cell
  • Spatial distribution
  • Tumor growth