scholarly journals Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse

2011 ◽  
Vol 121 (5) ◽  
pp. 2000-2012 ◽  
Author(s):  
Dontscho Kerjaschki ◽  
Zsuzsanna Bago-Horvath ◽  
Margaretha Rudas ◽  
Veronika Sexl ◽  
Christine Schneckenleithner ◽  
...  
2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Manar A. Abdul-Aziz ◽  
Amina K. Amin ◽  
Dalia H. El-Rouby ◽  
Olfat G. Shaker

Background.Oral squamous cell carcinoma (OSCC) is the most common oral malignancy that preferentially spreads to the cervical lymph node which, when involved, complicates the anticancer therapy and threatens the patient life. It was suggested that lymph node metastasis may be facilitated by lymphangiogenesis. VEGF-C is one of the most important lymphangiogenic inducers that promotes the lymphatic vessels growth and supports the survival of adult lymphatic endothelial cells.Methods. Lymphatic vessels density (LVD) and LV morphometry were digitally evaluated using D2-40. The expression of VEGF-C was also assessed using immunohistochemistry and real-time polymerase chain reaction in 6 normal oral mucosa cases and 72 cases of OSCC. The correlation between LVD and LV morphometry, VEGF-C, and lymph node metastasis was statistically assessed.Results. A positive cytoplasmic expression of VEGF-C was detected in both epithelial and connective tissue cells in 97% of OSCC, while all normal tissues reacted negatively. A greater expression of VEGF-C was associated with larger and more dilated LV and lymph node metastasis but not with LVD.Conclusion. VEGF-C is actively involved in the invasion and metastasis of OSCC via inducing morphological changes in LV. VEGF-C may be a promising target for anticancer therapy.


2018 ◽  
Vol 38 (10) ◽  
pp. 1972-1980
Author(s):  
Carlos H.C. Vieira-Filho ◽  
Stella M. Barrouin-Melo ◽  
Karine A. Damasceno ◽  
Márcio S.S. Araújo ◽  
Natalie F. Borges ◽  
...  

ABSTRACT: The inflammatory infiltrate in the tumor microenvironment, particularly in mammary tumors, has aroused great interest in oncology, to play different roles in the progression or tumor regression dependent on the types and cell subsets involved. The present study aimed to evaluate (1) the occurrence and intensity of macrophage infiltration in the mammary carcinoma microenvironment, (2) the expression of SOCS1 and SOCS3 proteins in tumor associated macrophages, (3) any association between these parameters and tumor development, as well as survival rates in female dogs. Twenty-two female dogs diagnosed as carcinoma arising in a mixed tumor (CMT) by histopathology were divided into two groups following mastectomy: dogs without metastasis (CMT(-)=11) and those with metastasis (CMT(+)=11). The following parameters were analyzed: tumor size, lymph node metastasis, clinical stage, histological grade, distribution and intensity of inflammatory infiltrate, tumor macrophage quantification by immunohistochemical analysis of SOCS1 and SOCS3 expression, and immunophenotyping of peripheral blood leukocytes by flow cytometry. Dogs with the higher proportions of macrophages in the inflammatory infiltrate (≥400/tumor) also had higher survival rates in comparison with dogs with less macrophages. Immunostaining revealed higher proportions of SOCS3-positive macrophages in dogs without lymph node metastasis, while SOCS1-positive macrophages were predominant in dogs with metastasis (p<0.05). Multivariate analysis found associations between survival rate and clinical staging (p=0.025), histological grade (p=0.007), and the expression of MHC-CI in circulating monocytes (p=0.018). Higher SOCS3 expression in activated macrophages within the inflammatory infiltrate were considered indicative of an antitumor immune response, improved clinicopathological parameters and longer survival, whereas SOCS1-related activation was associated with tumor progression, metastasis development and reduced survival in female dogs with mammary carcinomas.


PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e55797 ◽  
Author(s):  
Li Li ◽  
Shiro Mori ◽  
Maya Sakamoto ◽  
Shoki Takahashi ◽  
Tetsuya Kodama

2002 ◽  
Vol 81 (1) ◽  
pp. 38-44 ◽  
Author(s):  
Santiago Giron ◽  
Agueda M. Tejera ◽  
Giselle V. Ripoll ◽  
Daniel E. Gomez ◽  
Daniel F. Alonso

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Yuko Ito ◽  
Masa-Aki Shibata ◽  
Nabil Eid ◽  
Junji Morimoto ◽  
Yoshinori Otsuki

Lymphangiogenesis and the expression of vascular endothelial cell growth factor C (VEGF-C) in tumors have been considered to be causally promoting lymphatic metastasis. There are only a few studies on lymphatic metastasis in immunocompetent allograft mouse models. To study the relationship between VEGF-C-mediated lymphangiogenesis and axillary lymph node metastasis, we used two mouse mammary carcinoma cell lines; the BJMC338 has a low metastatic propensity, whereas the BJMC3879 has a high metastatic propensity although it originated from the former cell line. Each cell line was injected separately into two groups of female BALB/cmice creatingin vivomammary cancer models. The expression level of VEGF-C in BJMC3879 was higher than BJMC338. As the parent cell line, BJMC3879-derived tumors showed higher expression of VEGF-C compared to BJMC338-derived tumors. This higher expression of VEGF-C in BJMC3879-derived tumors was associated with marked increase in infiltrating macrophages and enhanced expression of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) reflecting increased tumoral lymphatic density and subsequent induction of axillary lymph node metastasis. Our mouse mammary carcinoma models are allotransplanted tumors showing the same axillary lymph node metastatic spectrum as human breast cancers. Therefore, our mouse models are ideal for exploring the various molecular mechanisms of cancer metastasis.


2011 ◽  
Vol 34 (1-2) ◽  
pp. 67-78 ◽  
Author(s):  
Aula Ammar ◽  
Rabab A. A. Mohammed ◽  
Marko Salmi ◽  
Michael Pepper ◽  
Emma C. Paish ◽  
...  

Background: Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1) in human breast tumors was used, along within vitrotechniques, to assess involvement in the metastatic process.Methods: 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC), CD209 (immature DC, iDC) and CD68 (macrophage, M&phis;).in vitroexpression of CLEVER-1 on lymphatic (LEC) and blood endothelial cells (BEC) was examined by flow cytometry.Results:in vitroresults showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples), lymphatic vessels (LV, 18.2% of samples) and in M&phis;/DCs (82.4% of samples). However, only CLEVER-1 expression in LV was associated with LN metastasis (p =0.027) and with M&phis; indices (p =0.021). Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p =0.049). The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001) and LV (p =0.004).Conclusions: The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN.


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