Lysophosphatidic Acid (LPA)-Induced Vascular Endothelial Growth Factor (VEGF) by Mesothelial Cells and Quantification of Host-Derived VEGF in Malignant Ascites

Sako, Akihiro; Kitayama, Joji; Shida, Dai; Suzuki, Rika; Sakai, Teruyuki; Ohta, Hiroyuki; Nagawa, Hirokazu

doi:10.1016/j.jss.2005.08.007

Cited by 21 publications

(14 citation statements)

References 52 publications

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“…TNFα and cAMP are examples and LPA Variants in MDR2 KO Murine HCC  serve as potential connections between the LPA/ATX/EDGR axis and HCC. There are many other potential links between LPA and HCC including but not limited to CTGF, TGF, and VEGF all of which are stimulated by LPA (46)(47)(48)(49)(50) and linked to HCC (51)(52)(53). These are all avenues for investigation of new treatment therapies; however, a expedited avenue would be to identify current FDA approved drugs that would benefit patients until dedicated treatments evolve.…”

Section: Resultsmentioning

confidence: 99%

Lysophosphatidic Acid Aberrancies and Hepatocellular Carcinoma: Studies in the MDR2 Gene Knockout Mouse

Skill

Xu³

et al. 2013

Cancer Investigation

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Studies show that lysophosphatidic acid (LPA) reprogramming is associated with the development of hepatocellular carcinoma (HCC). This manuscript evaluates the MDR2(-/-) model of HCC as a tool to examine the role of LPA reprogramming in the initiation/progression of HCC and identify novel treatment targets. Hepatic tumors developed in MDR2(-/-) mice between 9-12 m and serum LPA levels were greater in MDR2(-/-) when compared to controls. Blocking LPA biosynthesis/signaling significantly reduced tumor burden. LPA biosynthesis/signaling plays an important role in murine MDR2(-/-) model and is potentially linked to regulation of TNFα or other cytokines that are relevant to high-risk patients.

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Section: Resultsmentioning

confidence: 99%

Lysophosphatidic Acid Aberrancies and Hepatocellular Carcinoma: Studies in the MDR2 Gene Knockout Mouse

Skill

Xu³

et al. 2013

Cancer Investigation

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“…Indeed the role of molecule-dependant cell-cell interactions (integrin β-1, CD44), secreted factors (interleukin 6 and 8, VEGF, FGF2, TGF-β) and matrix metalloproteinases, has been illustrated in several reports [26]–[30]. However one of the most important partners of cancer cells in the peritoneum are mesothelial cells of the peritoneal surface.…”

Section: Discussionmentioning

confidence: 99%

Oncologic Trogocytosis of an Original Stromal Cells Induces Chemoresistance of Ovarian Tumours

et al. 2008

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BackgroundThe microenvironment plays a major role in the onset and progression of metastasis. Epithelial ovarian cancer (EOC) tends to metastasize to the peritoneal cavity where interactions within the microenvironment might lead to chemoresistance. Mesothelial cells are important actors of the peritoneal homeostasis; we determined their role in the acquisition of chemoresistance of ovarian tumours.Methodology/Principal FindingsWe isolated an original type of stromal cells, referred to as “Hospicells” from ascitis of patients with ovarian carcinosis using limiting dilution. We studied their ability to confer chemoresistance through heterocellular interactions. These stromal cells displayed a new phenotype with positive immunostaining for CD9, CD10, CD29, CD146, CD166 and Multi drug resistance protein. They preferentially interacted with epithelial ovarian cancer cells. This interaction induced chemoresistance to platin and taxans with the implication of multi-drug resistance proteins. This contact enabled EOC cells to capture patches of the Hospicells membrane through oncologic trogocytosis, therefore acquiring their functional P-gp proteins and thus developing chemoresistance. Presence of Hospicells on ovarian cancer tissue micro-array from patients with neo-adjuvant chemotherapy was also significantly associated to chemoresistance.Conclusions/SignificanceThis is the first report of trogocytosis occurring between a cancer cell and an original type of stromal cell. This interaction induced autonomous acquisition of chemoresistance. The presence of stromal cells within patient's tumour might be predictive of chemoresistance. The specific interaction between cancer cells and stromal cells might be targeted during chemotherapy.

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“…The maximum abdominal circumference was measured with a measuring tape by two investigators who were blinded as to which group the animal had been assigned [24]. Because mice had only a small amount of ascites, 1 mL of PBS was intraperitoneally injected and the peritoneal fluid was totally recovered [25]. We also examined the total number and weight of peritoneal tumors in the mesenterium of each mouse according to Ueda et al [26].…”

Section: Preparation Of Murine Peritoneal Metastasis Modelmentioning

confidence: 99%

Effect of Bevacizumab, a Humanized Monoclonal Antibody to Vascular Endothelial Growth Factor, on Peritoneal Metastasis of MNK-45P Human Gastric Cancer in Mice

Ninomiya

Ito

Tajima

et al. 2009

Journal of Surgical Research

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Lysophosphatidic Acid (LPA)-Induced Vascular Endothelial Growth Factor (VEGF) by Mesothelial Cells and Quantification of Host-Derived VEGF in Malignant Ascites

Cited by 21 publications

References 52 publications

Lysophosphatidic Acid Aberrancies and Hepatocellular Carcinoma: Studies in the MDR2 Gene Knockout Mouse

Lysophosphatidic Acid Aberrancies and Hepatocellular Carcinoma: Studies in the MDR2 Gene Knockout Mouse

Oncologic Trogocytosis of an Original Stromal Cells Induces Chemoresistance of Ovarian Tumours

Effect of Bevacizumab, a Humanized Monoclonal Antibody to Vascular Endothelial Growth Factor, on Peritoneal Metastasis of MNK-45P Human Gastric Cancer in Mice

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