Top

Published in:

01-02-2017 | Original Article

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

Authors: Diego Guidolin, Christian Marinaccio, Cinzia Tortorella, Tiziana Annese, Simona Ruggieri, Nicoletta Finato, Enrico Crivellato, Domenico Ribatti

Published in: Clinical and Experimental Medicine | Issue 1/2017

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.

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.PubMed

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

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

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.CrossRef

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.PubMed

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.PubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

16.

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

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

29.

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

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRef

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRef

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.CrossRefPubMed

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.

38.

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

39.

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

40.

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

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.CrossRef

42.

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

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.CrossRefPubMed

Title: Non-random spatial relationships between mast cells and microvessels in human endometrial carcinoma
Authors: Diego Guidolin
Christian Marinaccio
Cinzia Tortorella
Tiziana Annese
Simona Ruggieri
Nicoletta Finato
Enrico Crivellato
Domenico Ribatti
Publication date: 01-02-2017
Publisher: Springer International Publishing
Published in: Clinical and Experimental Medicine / Issue 1/2017
Print ISSN: 1591-8890
Electronic ISSN: 1591-9528
DOI: https://doi.org/10.1007/s10238-016-0407-4

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2017

Overexpression of miR-664 is associated with enhanced osteosarcoma cell migration and invasion ability via targeting SOX7

Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer

Clinicopathological and prognostic significance of chemokine receptor CXCR4 in patients with bone and soft tissue sarcoma: a meta-analysis

CDKN1A histone acetylation and gene expression relationship in gastric adenocarcinomas

Long non-coding RNA CARLo-5 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients

X-linked ectodermal dysplasia receptor (XEDAR) gene silencing prevents caspase-3-mediated apoptosis in Sjögren’s syndrome

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page