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Oncologic trogocytosis of an original stromal cells induces chemoresistance of ovarian tumours.

Rafii A, Mirshahi P, Poupot M, Faussat AM, Simon A, Ducros E, Mery E, Couderc B, Lis R, Capdet J, Bergalet J, Querleu D, Dagonnet F, Fournié JJ, Marie JP, Pujade-Lauraine E, Favre G, Soria J, Mirshahi M - PLoS ONE (2008)

Bottom Line: Presence of Hospicells on ovarian cancer tissue micro-array from patients with neo-adjuvant chemotherapy was also significantly associated to chemoresistance.This interaction induced autonomous acquisition of chemoresistance.The specific interaction between cancer cells and stromal cells might be targeted during chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: UMRS 872 INSERM, Université Pierre et Marie Curie-Paris 6 and Université Paris Descartes, Equipe 18, Centre de Recherche des Cordeliers, Paris, France.

ABSTRACT

Background: The 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 findings: We 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/significance: This 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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Clinical relevance of the presence of Hospicells among ovarian cancer tumors.Tissue Micro-arrays were prepared from tumors originating from 29 patients who underwent a neo-adjuvant chemotherapy. A. Different densities of Hospicells as represented by CD10 staining. Morphological controls were used to rule out the staining of endothelial cells. B. Samples from chemoresistant patients had significantly higher density of Hospicells compared to chemosensitive patients (* p<0.05). Three different spots were used to characterize the Hospicells' density for each patient.
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pone-0003894-g008: Clinical relevance of the presence of Hospicells among ovarian cancer tumors.Tissue Micro-arrays were prepared from tumors originating from 29 patients who underwent a neo-adjuvant chemotherapy. A. Different densities of Hospicells as represented by CD10 staining. Morphological controls were used to rule out the staining of endothelial cells. B. Samples from chemoresistant patients had significantly higher density of Hospicells compared to chemosensitive patients (* p<0.05). Three different spots were used to characterize the Hospicells' density for each patient.

Mentions: A total of 29 ovarian carcinomas were assessed histopathologically for a Hospicells infiltrate within the tumor using a CD10 staining. Figure 8A displays the different level of Hospicells staining. As displayed in Figure 8B TMA from chemoresistant patients had significantly higher density of Hospicells compared to chemosensitive patients. Demographic characteristics of the patients included in the study are displayed in Figure 8C.


Oncologic trogocytosis of an original stromal cells induces chemoresistance of ovarian tumours.

Rafii A, Mirshahi P, Poupot M, Faussat AM, Simon A, Ducros E, Mery E, Couderc B, Lis R, Capdet J, Bergalet J, Querleu D, Dagonnet F, Fournié JJ, Marie JP, Pujade-Lauraine E, Favre G, Soria J, Mirshahi M - PLoS ONE (2008)

Clinical relevance of the presence of Hospicells among ovarian cancer tumors.Tissue Micro-arrays were prepared from tumors originating from 29 patients who underwent a neo-adjuvant chemotherapy. A. Different densities of Hospicells as represented by CD10 staining. Morphological controls were used to rule out the staining of endothelial cells. B. Samples from chemoresistant patients had significantly higher density of Hospicells compared to chemosensitive patients (* p<0.05). Three different spots were used to characterize the Hospicells' density for each patient.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2597737&req=5

pone-0003894-g008: Clinical relevance of the presence of Hospicells among ovarian cancer tumors.Tissue Micro-arrays were prepared from tumors originating from 29 patients who underwent a neo-adjuvant chemotherapy. A. Different densities of Hospicells as represented by CD10 staining. Morphological controls were used to rule out the staining of endothelial cells. B. Samples from chemoresistant patients had significantly higher density of Hospicells compared to chemosensitive patients (* p<0.05). Three different spots were used to characterize the Hospicells' density for each patient.
Mentions: A total of 29 ovarian carcinomas were assessed histopathologically for a Hospicells infiltrate within the tumor using a CD10 staining. Figure 8A displays the different level of Hospicells staining. As displayed in Figure 8B TMA from chemoresistant patients had significantly higher density of Hospicells compared to chemosensitive patients. Demographic characteristics of the patients included in the study are displayed in Figure 8C.

Bottom Line: Presence of Hospicells on ovarian cancer tissue micro-array from patients with neo-adjuvant chemotherapy was also significantly associated to chemoresistance.This interaction induced autonomous acquisition of chemoresistance.The specific interaction between cancer cells and stromal cells might be targeted during chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: UMRS 872 INSERM, Université Pierre et Marie Curie-Paris 6 and Université Paris Descartes, Equipe 18, Centre de Recherche des Cordeliers, Paris, France.

ABSTRACT

Background: The 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 findings: We 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/significance: This 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.

Show MeSH
Related in: MedlinePlus