Abstract
PURPOSE: The aim of this study was to determine why colorectal tumors confined to submucosa rarely metastasize. Under normal conditions, the submucosa contains many large lymphatic vessels with thin walls that would presumably favor the spread of cancer cells through the lymphatic system. METHODS: Specimens of colorectal cancer tissue, the border between tumor and normal tissue, and normal tissue were obtained from patients undergoing radical resection of colorectal cancer. The material was embedded in methacrylate resin for light microscopy and Epon® for transmission electron microscopy examination. Light microscopy observations were routinely performed on serial sections. RESULTS: No lymphatic vessels were ever found in the tumor mass. The border area contained peritumoral inflammatory infiltrate of variable thickness. Where submucosal lymphatic vessels came into contact with peritumoral inflammatory infiltrate, they were profoundly altered: their endothelium was fragmented, and their walls were disrupted. These altered lymphatic vessels were almost always accompanied by mast cells, which were observed in the process of degranulating toward the lymphatic endothelium. No such alterations were detected in blood vessels. CONCLUSION: Our results suggest that mast cells, probably influenced by inflammatory infiltrate and/or colorectal cancer cells, destroy lymphatic vessels, which prevents cancer cells from spreading through the lymphatic system.
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References
JP Sleeman J Krishnan V Kirkin P Baumann (2001) ArticleTitleMarkers for the lymphatic endothelium Microsc Res Tech 55 61–69
G Sacchi E Weber M Aglianò N Raffaelli L Comparini (1997) ArticleTitleThe structure of superficial lymphatics in the human thigh Anat Rec 247 53–62
G Sacchi E Weber M Aglianò N Cavina L Comparini (1999) ArticleTitleLymphatic vessels of the human heart J Submicrosc Cytol Pathol 31 515–525
CM Fenoglio GI Kaye N Lane (1973) ArticleTitleDistribution of human colonic lymphatics in normal, hyperplastic, and adenomatous tissue Gastroenterology 64 51–66
D Blumberg PB Paty JG Guillem et al. (1999) ArticleTitleAll patients with small intramural rectal cancers are at risk for lymph node metastasis Dis Colon Rectum 42 881–885
I Carr P Watson NM Pettigrew (1989) ArticleTitleMechanisms of invasion and lymphatic penetration in human colorectal cancer Clin Exp Metastasis 7 507–516
J White PW Hewett T McCulloch K Alitalo JC Murray J Carmichael (2000) ArticleTitleExpression of FLT-4 (VEGFR-3) in colorectal cancer Proc Am Assoc Cancer Res 41 88–516
V Joukov K Pajusola A Kaipainen et al. (1996) ArticleTitleA novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases EMBO J 15 290–298
M Jeltsch A Kaipainen V Joukov et al. (1997) ArticleTitleHyperplasia of lymphatic vessels in VEGF-C transgenic mice Science 276 1423–1425
E Kukk A Lymboussaki S Taira et al. (1996) ArticleTitleVEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development Development 122 3829–3837
SJ Oh MM Jeltsch R Birkenhager et al. (1997) ArticleTitleVEGF and VEGF-C Dev Biol 188 96–109
M Orlandini L Marconcini R Ferruzzi S Oliviero (1996) ArticleTitleIdentification of a c-fos-induced gene that is related to the platelet-derived growth factor/vascular endothelial growth factor family Proc Natl Acad Sci U S A 93 11675–80
L Jussila R Valtola TA Partanen et al. (1998) ArticleTitleLymphatic endothelium and Kaposi’s sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor 3 Cancer Res 58 1599–1604
TA Partanen J Arola A Saaristo et al. (2000) ArticleTitleVEGF-C and VEGF-D expression in neuroendocrine cells and their receptor, VEGFR-3, in fenestrated blood vessels in human tissue FASEB J 14 2087–2096
K Akagi Y Ikeda M Miyazaki et al. (2000) ArticleTitleVascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues Br J Cancer 83 887–891
RM de Waal MC van Altena H Erhard UH Weidle PT Nooijen DJ Ruiter (1997) ArticleTitleLack of lymphangiogenesis in human primary cutaneous melanoma Am J Pathol 150 1951–1957
AJ Leu DA Berk A Lymboussaki K Alitalo RK Jain (2000) ArticleTitleAbsence of functional lymphatics within a murine sarcoma Cancer Res 60 4324–4327
T Karpanen M Egeblad MJ Karkkainen et al. (2001) ArticleTitleVascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth Cancer Res 61 1786–1790
MS Pepper (2001) ArticleTitleLymphangiogenesis and tumor metastasis Clin Cancer Res 7 462–468
JR Jass WS Atkin J Cuzick et al. (1986) ArticleTitleThe grading of rectal cancer Histopathology 10 437–459
S Foulds CH Wakefield M Giles J Gillespie JF Dye PJ Guillou (1993) ArticleTitleExpression of a suppressive p15E-related epitope in colorectal and gastric cancer Br J Cancer 68 610–616
TB Halvorsen E Seim (1989) ArticleTitleAssociation between invasiveness, inflammatory reaction, desmoplasia and survival in colorectal cancer J Clin Pathol 42 162–166
HJ Nielsen U Hansen IJ Christensen et al. (1999) ArticleTitleIndependent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue J Pathol 189 487–495
MJ Fernandez-Acenero M Galindo-Gallego J Sanz A Aljama (2000) ArticleTitlePrognostic influence of tumor-associated eosinophilic infiltrate in colorectal carcinoma Cancer 88 1544–1548
T Ishizuka Y Okayama H Kobayashi M Mori (1999) ArticleTitleInterleukin-3 production by mast cells from human lung Inflammation 23 25–35
M Tomita Y Matsuzaki T Onitsuka (1999) ArticleTitleCorrelation between mast cells and survival rates in patients with pulmonary adenocarcinoma Lung Cancer 26 103–108
J Sorbo A Jakobsson K Norby (1994) ArticleTitleMast-cell histamine is angiogenic through receptors for histamine1 and histamine2 Int J Exp Path 75 43–50
Z Qu JM Liebler MR Powers et al. (1995) ArticleTitleMast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma Am J Pathol 147 564–573
RJ Blair H Meng MJ Marchese et al. (1997) ArticleTitleHuman mast cells stimulate vascular tube formation. Tryptase is a novel potent angiogenic factor J Clin Invest 99 2691–2700
A Grutzkau S Kruger-Krasagakes H Baumeister et al. (1998) ArticleTitleSynthesis, storage, and release of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) by human mast cells Mol Biol Cell 9 875–884
L Fan S Iseki (1999) ArticleTitleImmunohistochemical localization of vascular endothelial growth factor in the globule leukocyte/mucosal mast cell of the rat respiratory and digestive tracts Histochem Cell Biol 111 13–21
LM Coussens WW Raymond G Bergers et al. (1999) ArticleTitleInflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis Genes Dev 13 1382–1397
L Schweigerer B Malerstein D Gospodarowicz (1987) ArticleTitleTumor necrosis factor inhibits the proliferation of cultured capillary endothelial cells Biochem Biophys Res Commun 143 997–1004
A Moller U Lippert D Lessmann et al. (1993) ArticleTitleHuman mast cells produce IL-81 J Immunol 151 3261–3266
SJ Compton JA Cairns ST Holgate AF Walls (2000) ArticleTitleHuman mast cell tryptase stimulates the release of an IL-8-dependent neutrophil chemotactic activity from human umbilical vein endothelial cells (HUVEC) Clin Exp Immunol 121 31–36
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Sacchi, G., Weber, E., Aglianó, M. et al. Lymphatic Vessels in Colorectal Cancer and Their Relation With Inflammatory Infiltrate. Dis Colon Rectum 46, 40–47 (2003). https://doi.org/10.1007/s10350-004-6494-4
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DOI: https://doi.org/10.1007/s10350-004-6494-4