Fibrin Deposition in Squamous Cell Carcinomas of the Larynx and Hypopharynx

1998 ◽  
Vol 80 (11) ◽  
pp. 767-772 ◽  
Author(s):  
Helga Bárdos ◽  
Attila Juhász ◽  
Gábor Répássy ◽  
Róza Ádány
Keyword(s):  
Monoclonal Antibody ◽  
Connective Tissue ◽  
Tumor Cell ◽  
Blood Vessels ◽  
Squamous Cell ◽  
Close Association ◽  
Squamous Cell Carcinomas ◽  
Coagulation Cascade ◽  
Fibrin Deposition ◽  
Tumor Blood Vessels

SummaryExtravascular fibrin deposition is frequently observed within and around neoplastic tissue and has been implicated in various aspects of tumor growth. The distribution of fibrin deposits was investigated in squamous cell carcinomas representing different stages of tumor progression of the larynx (n = 25) and hypopharynx (n = 9) by immunofluorescent techniques. Double and treble labelings were used to detect fibrinogen and fibrin in combination with marker antigens for tumor cells (cytokeratin), endothelial cells (von Willebrand factor), macrophages (recognized by KiM7), as well as factor XIII subunit A (FXIIIA) and tenascin (an embryonic extracellular matrix protein newly expressed during tumorigenesis). All tissue samples showed specific staining for fibrinogen/fibrin. Fibrin deposition was localized almost exclusively in the connective tissue compartment of tumors with characteristic accumulation at the interface of connective tissue and the tumorous parenchyma. In certain tumor samples showing highly invasive characteristics, fibrin deposits were observed in close association with tumor blood vessels in the tumor cell nodules. The overlapping reactions with polyclonal antibody to fibrinogen/fibrin and monoclonal antibody to fibrin indicate the activation of the coagulation cascade resulting in in situ thrombin activation and fibrin formation. Fibrin was crosslinked and stabilized by FXIIIA as revealed by urea insolubility test. Accumulation of phagocytozing macrophages detected by Ki M7 monoclonal antibody could be seen in areas of fibrin deposition. The blood coagulation factor XIIIA was detected in and around the cells labeled with Ki M7 antibody. Tenascin and fibrin deposits were found in the same localization in the tumor stroma and in association with tumor blood vessels within the tumor cell nodules. Neither fibrin nor tenascin were detected in the histologically normal tissue adjacent to tumors. The close association between fibrin deposits and macrophage accumulation strongly suggests the active participation of tumor-associated macrophages in the formation of stabilized intratumoral fibrin that facilitates tumor matrix generation and tumor angiogenesis.

The Molecular and Cellular Processes of Tumor Cell-Mediated Tumor Angiogenesis and Vasculogenesis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3267-3267
Author(s):  
Quansheng Zhou ◽  
Zhifei Cao ◽  
Meimei Bao ◽  
Graduate student ◽  
Bingxue Shang ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Signaling Pathways ◽  
Blood Vessels ◽  
Tumor Cells ◽  
Erk Signaling ◽  
Tumor Cell Lines ◽  
Tumor Neovascularization ◽  
Tumor Blood Vessels

Abstract Abstract 3267 It is well known that tumors make blood vessels through endothelial cell-mediated angiogenesis; whereas, increasing data have shown that tumor cell-mediated vasculogenesis plays an important role in tumor neovascularization in a variety of high metastatic malignant tumors, but the mechanisms are largely unknown. We previously established new models for studying the mechanisms of tumor angiogenesis and vasculogenesis (Zhou Q. et al. Method 44(2):190–195, 2008; Zhou Q, et al. Nature: Structure and Molecular Biology 2010, 17:57–62). Using in vitro tube formation system and in vivo mouse tumor xenografts, we have recently tested the vasculogenic capability of 85 tumor cell lines and studied the molecular and cellular processes of tumor cell-mediated tumor neovascularization. Among 62 human tumor cell lines tested, 25 of them were able to directly form capillary-like tubes in vitro and tumor blood vessels in vivo tumor xenografts, while 10 out of 23 mouse tumor cell lines displayed tube-forming and vasculogenic capabilities. Notably, these vasculogenic tumor cells were mostly derived from high metastatic and aggressive tumors, including pre-cancerous stem cells, cancer stem cells, high metastatic tumor cells, and tumor endothelial cells. Utilizing DNA microarray, tumor tissue array, RT-PCR, western blotting, and immunofluorescient staining, we observed that 15 genes were highly expressed in vasculogenic cancer stem cells and various tumor cells; among them, 4 genes did not expressed in all of the 15 normal human tissues while other 11 genes were only expressed in the testis, but absent in other normal tissues. Additionally, many embryonic angiogenic and vasculogenic genes were overexpressed in the vasculogenic tumor cells, implying that these genes may play an important role in tumor vasculogenesis. Accordingly, we raise a hypothetic model that endogenous and exogenous factors induce tumor cells to express a variety of angiogenic and vasculogenic genes which drive the vasculogenic tumor cells to connect each other and to interact with endothelial cells and various blood cells, resulting in generation of tumor blood vessels. Furthermore, we explored the role and mechanism of human ovarian cancer Hey1B cell-mediated tumor neovascularization. Herein, for the first time we found that Hey1B cells directly formed capillary tubular structure in vitro independent of any growth factors and functional tumor blood vessels in vivo tumor xenografts. Moreover, we observed that more than 30 angiogenic and vasculogenic genes were overexpressed in the cells and the tumor tissues, including VE-cadherin, FGFR1, VEGFA, HIF1A, Sema4D, plexinB1, EphB2, NOTCH1, ROBO4, Ephrin B2, SFRP1, MAFB, SOX17, WIPF2, MAGEF1, MAGED1, New3, ZFP106, RUNX1, and other 16 poorly annotated genes, while Akt and ERK signaling pathways were found to be over activated in Hey1B cells and the tumor tissues. This valuable information gets new insight into the mechanisms of tumor cell-predominant neovascularization. Using Hey1B cells as tumor vasculogenic model, we screened anti-tumor vasculogenic small molecules in the traditional Chinese herbal medicinal library and found that lycorine hydrochloride (LH) effectively inhibited Hey1B cell-mediated tube formation in vitro, blood vessel generation and tumor growth in vivo. Molecular mechanism analysis showed that LH markedly inhibited the expression of VE-cadherin, Sema4D, FGFR1, VEGFA, NOTCH1 and SFRP1 genes, and it also blocked Akt and ERK signaling pathways. Taken together, a varieties of angiogenic and vasculogenic genes are overexpressed in angiogenic and vasculogenic tumor cells, meanwhile, Akt and ERK signaling pathways were activated in the vasculogenic tumor cells tested; and that LH effectively suppresses ovarian cancer neovascularization and tumor growth through inhibition of several key genes and signaling pathways. Therefore, angiogenic and vasculogenic genes and tumor cells are good targets for novel anti-tumor vasculogenesis and anti-tumor drug discovery. Disclosures: No relevant conflicts of interest to declare.

Antitumor Effects of a Monoclonal Antibody that Binds Anionic Phospholipids on the Surface of Tumor Blood Vessels in Mice

2005 ◽  
Vol 11 (4) ◽  
pp. 1551-1562 ◽  
Author(s):  
Sophia Ran ◽  
Jin He ◽  
Xianming Huang ◽  
Melina Soares ◽  
Douglas Scothorn ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Blood Vessels ◽  
Antitumor Effects ◽  
Anionic Phospholipids ◽  
Tumor Blood Vessels
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