Exosome Transfer Between Pancreatic-cancer Cells Is Associated With Metastasis in a Nude-mouse Model

2021 ◽  
Vol 41 (6) ◽  
pp. 2829-2834
Author(s):  
HIRONAO ICHIKAWA ◽  
ATSUSHI SUETSUGU ◽  
TOMOYUKI SATAKE ◽  
HITOMI AOKI ◽  
TAKAHIRO KUNISADA ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Nude Mouse ◽  
Nude Mouse Model ◽  
Pancreatic Cancer Cells

scholarly journals Mesothelin blockage by Amatuximab suppresses cell invasiveness, enhances gemcitabine sensitivity and regulates cancer cell stemness in mesothelin-positive pancreatic cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fumihiko Matsuzawa ◽  
Hirofumi Kamachi ◽  
Tatsuzo Mizukami ◽  
Takahiro Einama ◽  
Futoshi Kawamata ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Morphological Changes ◽  
Pancreatic Cancer Cells ◽  
Cell Invasiveness ◽  
And Migration ◽  
Migration Capacity

Abstract Background Mesothelin is a 40-kDa glycoprotein that is highly overexpressed in various types of cancers, however molecular mechanism of mesothelin has not been well-known. Amatuximab is a chimeric monoclonal IgG1/k antibody targeting mesothelin. We recently demonstrated that the combine therapy of Amatuximab and gemcitabine was effective for peritonitis of pancreatic cancer in mouse model. Methods We discover the role and potential mechanism of mesothelin blockage by Amatuximab in human pancreatic cells both expressing high or low level of mesothelin in vitro experiment and peritonitis mouse model of pancreatic cancer. Results Mesothelin blockage by Amatuximab lead to suppression of invasiveness and migration capacity in AsPC-1 and Capan-2 (high mesothelin expression) and reduce levels of pMET expression. The combination of Amatuximab and gemcitabine suppressed proliferation of AsPC-1 and Capan-2 more strongly than gemcitabine alone. These phenomena were not observed in Panc-1 and MIA Paca-2 (Mesothelin low expression). We previously demonstrated that Amatuximab reduced the peritoneal mass in mouse AsPC-1 peritonitis model and induced sherbet-like cancer cell aggregates, which were vanished by gemcitabine. In this study, we showed that the cancer stem cell related molecule such as ALDH1, CD44, c-MET, as well as proliferation related molecules, were suppressed in sherbet-like aggregates, but once sherbet-like aggregates attached to peritoneum, they expressed these molecules strongly without the morphological changes. Conclusions Our work suggested that Amatuximab inhibits the adhesion of cancer cells to peritoneum and suppresses the stemness and viability of those, that lead to enhance the sensitivity for gemcitabine.

A Novel Nude Mouse Model of Liver Metastasis and Peritoneal Dissemination From the Same Human Pancreatic Cancer Line

Pancreas ◽  
2002 ◽  
Vol 24 (3) ◽  
pp. 242-250 ◽  
Author(s):  
Hidefumi Nishimori ◽  
Takahiro Yasoshima ◽  
Fumitake Hata ◽  
Ryuichi Denno ◽  
Yoshiyuki Yanai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Mouse Model ◽  
Nude Mouse ◽  
Peritoneal Dissemination ◽  
Human Pancreatic Cancer ◽  
Nude Mouse Model ◽  
Cancer Line

Cancer-Associated Thrombosis: Cancer Cell-Derived Microparticles As a Trigger of Venous Thrombosis in a Mouse Model of Flow Restriction

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 34-34
Author(s):  
Grace M. Thomas ◽  
Alexander Brill ◽  
Denisa D. Wagner
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Venous Thrombosis ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Flow Restriction ◽  
Tumor Bearing ◽  
Pancreatic Cancer Cells ◽  
Venous Thromboembolic Events ◽  
Cancer Associated Thrombosis

Abstract Abstract 34 Thrombotic complications are common side effects in cancer patients and up to 20% of all symptomatic cases of deep vein thrombosis (DVT) are thought to be cancer-related. Since Armand Trousseau established a direct correlation between thrombophlebitis and cancer in 1865, cancer-associated thrombosis has been the focus of several studies. All tumor types are associated with thrombosis but the incidence is particularly high (up to 57%) in patients suffering from pancreatic cancer (Sack et al Medicine 1977; Blom et al Eur J Cancer 2006; Cronin-Fenton et al Br J Cancer 2010). Cancer cells shed procoagulant microparticles (MPs) that can reach the bloodstream of pancreatic tumor-bearing mice and of patients with pancreatic cancer (Thomas et al J Exp Med 2009, Zwicker et al Thromb Res 2009). At their surface, these vesicles express a higher density of active tissue factor (TF) when compared to their parental cell (> 100-fold), and were shown to contribute to vessel injury-induced thrombosis (Thomas et al J Exp Med 2009). Furthermore, the concentration of circulating TF-bearing tumor-derived MPs has been correlated with cancer-associated venous thromboembolic events in patients (Del Conde et al J Thromb Haem 2007; Hron et al Thromb Haemost 2007; Langer et al Ann Hematol 2008; Zwicker et al Thromb Res 2009). In this study, we addressed experimentally whether circulating tumor microparticles play a role in DVT associated with cancer. We used a mouse model of DVT where thrombosis is induced by flow restriction (90% reduction in the lumen size) of the inferior vena cava (IVC) (Brill et al Blood 2010). In contrast to most DVT models, this model maintains blood flow in the IVC and it does not induce injury or endothelial denudation and thus is suitable for comparisons to human patients. The DVT model was used in combination with a model of murine pancreatic cancer (Thomas et al J Exp Med 2009). We observed that all the mice implanted subcutaneously with pancreatic cancer cells (Panc02 cell line) and submitted 35 days later to partial flow restriction of the IVC (n=8) developed an occlusive thrombus after 3 hours of flow restriction, while only 2 out of 7 control mice did (P < 0.05). We observed in this DVT model that mice infused with cancer cell-derived MPs have the same phenotype as the tumor-bearing mice since 100% of them developed a thrombus (P < 0.05 when compared to control mice), indicating that circulating tumoral microparticles play an important part in the triggering of cancer-associated DVT. A pro-thrombotic effect could be observed as early as 1 hour after stenosis in cancer cell-derived MPs-injected mice (P < 0.05 when compared to control mice). Moreover, thrombus formation after 1 hour of stenosis could be abolished when mice were pretreated with hirudin, suggesting the importance of the MP-generated thrombin likely by MP-derived TF activity. In conclusion, our results support the hypothesis that tumoral microparticles trigger cancer-associated venous thrombosis. Thus targeting their recruitment or activity could help to prevent cancer-associated DVT and its complication, pulmonary embolism. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Matrilysin (MMP-7) induces homotypic adhesion of human colon cancer cells and enhances their metastatic potential in nude mouse model

Oncogene ◽  
2003 ◽  
Vol 22 (54) ◽  
pp. 8662-8670 ◽  
Author(s):  
Mitomu Kioi ◽  
Kazuhiro Yamamoto ◽  
Shouichi Higashi ◽  
Naohiko Koshikawa ◽  
Kiyohide Fujita ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Nude Mouse ◽  
Human Colon ◽  
Metastatic Potential ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Nude Mouse Model ◽  
Human Colon Cancer Cells
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