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Ascites-derived pancreatic ductal adenocarcinoma primary cell cultures as a platform for personalised medicine.

Golan T, Atias D, Barshack I, Avivi C, Goldstein RS, Berger R - Br. J. Cancer (2014)

Bottom Line: Ascites-derived PDAC primary cells were isolated, cultured and characterised in ovo and in vitro.The tumorigenicity and invasiveness of the cells were demonstrated in vivo using chicken chorioallantoic membrane grafts.This model has the potential to study signalling pathways in PDAC progression and to evaluate targeted therapies for the individual patient expeditiously, thereby supporting personalised treatment decisions.

View Article: PubMed Central - PubMed

Affiliation: 1] Institute of Oncology, Sheba Medical Center, Tel Hashomer 52621, Israel [2] Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.

ABSTRACT

Background: Challenges in developing drugs for pancreatic ductal adenocarcinoma (PDAC) include obtaining metastatic cancer tissue for research and validating biomarkers predicative for personalised therapeutic decisions. We have recently developed a novel therapeutic model for PDAC to address these challenges based on the isolation of viable PDAC cells derived from ascites fluid.

Methods: Ascites fluid was obtained from PDAC patients undergoing palliative paracentesis. Ascites-derived PDAC primary cells were isolated, cultured and characterised in ovo and in vitro.

Results: We successfully established ascites-derived primary cell cultures within 2-7 days from 92% (93 out of 101) of the ascites fluid samples obtained (from 36 different patients). Homogeneous epithelial PDAC-enriched cell cultures were identified and characterised. We observed a wide range in doubling times and migration properties among the different patient-derived cell cultures. The diverse nature of each individual patient's cell cultures was further demonstrated by differences in therapeutic susceptibility and resistance. The tumorigenicity and invasiveness of the cells were demonstrated in vivo using chicken chorioallantoic membrane grafts.

Conclusions: We have developed a unique ascites-derived PDAC primary cell culture model. This model has the potential to study signalling pathways in PDAC progression and to evaluate targeted therapies for the individual patient expeditiously, thereby supporting personalised treatment decisions.

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Ascites-derived PDAC primary cultures' functional characteristics. (A) Growth curve of PDAC primary cells from eight different patients. (B) Varying migration properties in two different patients during the progression of their disease is shown. A significant increase in migration activity was observed during diseases progression. Values represent the means±s.d. (*P<0.05). (C) Varying invasive properties in six different cultures from five different patients is depicted. In cell cultures displaying spindle-like morphology, a significantly higher fraction of cells with invasion properties was observed. Values represent the means±s.d. (*P<0.05).
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fig2: Ascites-derived PDAC primary cultures' functional characteristics. (A) Growth curve of PDAC primary cells from eight different patients. (B) Varying migration properties in two different patients during the progression of their disease is shown. A significant increase in migration activity was observed during diseases progression. Values represent the means±s.d. (*P<0.05). (C) Varying invasive properties in six different cultures from five different patients is depicted. In cell cultures displaying spindle-like morphology, a significantly higher fraction of cells with invasion properties was observed. Values represent the means±s.d. (*P<0.05).

Mentions: To study functional characteristics of the ascites-isolated cells from PDAC patients, we compared the doubling time between cultures from eight different patients and an established cell line (PANC-1). The patients' cultures demonstrated varying proliferation rates (Figure 2A). In all of the cultures the rate was lower (range 7–14 days) when compared with PANC-1 (1.5 days).


Ascites-derived pancreatic ductal adenocarcinoma primary cell cultures as a platform for personalised medicine.

Golan T, Atias D, Barshack I, Avivi C, Goldstein RS, Berger R - Br. J. Cancer (2014)

Ascites-derived PDAC primary cultures' functional characteristics. (A) Growth curve of PDAC primary cells from eight different patients. (B) Varying migration properties in two different patients during the progression of their disease is shown. A significant increase in migration activity was observed during diseases progression. Values represent the means±s.d. (*P<0.05). (C) Varying invasive properties in six different cultures from five different patients is depicted. In cell cultures displaying spindle-like morphology, a significantly higher fraction of cells with invasion properties was observed. Values represent the means±s.d. (*P<0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4007225&req=5

fig2: Ascites-derived PDAC primary cultures' functional characteristics. (A) Growth curve of PDAC primary cells from eight different patients. (B) Varying migration properties in two different patients during the progression of their disease is shown. A significant increase in migration activity was observed during diseases progression. Values represent the means±s.d. (*P<0.05). (C) Varying invasive properties in six different cultures from five different patients is depicted. In cell cultures displaying spindle-like morphology, a significantly higher fraction of cells with invasion properties was observed. Values represent the means±s.d. (*P<0.05).
Mentions: To study functional characteristics of the ascites-isolated cells from PDAC patients, we compared the doubling time between cultures from eight different patients and an established cell line (PANC-1). The patients' cultures demonstrated varying proliferation rates (Figure 2A). In all of the cultures the rate was lower (range 7–14 days) when compared with PANC-1 (1.5 days).

Bottom Line: Ascites-derived PDAC primary cells were isolated, cultured and characterised in ovo and in vitro.The tumorigenicity and invasiveness of the cells were demonstrated in vivo using chicken chorioallantoic membrane grafts.This model has the potential to study signalling pathways in PDAC progression and to evaluate targeted therapies for the individual patient expeditiously, thereby supporting personalised treatment decisions.

View Article: PubMed Central - PubMed

Affiliation: 1] Institute of Oncology, Sheba Medical Center, Tel Hashomer 52621, Israel [2] Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.

ABSTRACT

Background: Challenges in developing drugs for pancreatic ductal adenocarcinoma (PDAC) include obtaining metastatic cancer tissue for research and validating biomarkers predicative for personalised therapeutic decisions. We have recently developed a novel therapeutic model for PDAC to address these challenges based on the isolation of viable PDAC cells derived from ascites fluid.

Methods: Ascites fluid was obtained from PDAC patients undergoing palliative paracentesis. Ascites-derived PDAC primary cells were isolated, cultured and characterised in ovo and in vitro.

Results: We successfully established ascites-derived primary cell cultures within 2-7 days from 92% (93 out of 101) of the ascites fluid samples obtained (from 36 different patients). Homogeneous epithelial PDAC-enriched cell cultures were identified and characterised. We observed a wide range in doubling times and migration properties among the different patient-derived cell cultures. The diverse nature of each individual patient's cell cultures was further demonstrated by differences in therapeutic susceptibility and resistance. The tumorigenicity and invasiveness of the cells were demonstrated in vivo using chicken chorioallantoic membrane grafts.

Conclusions: We have developed a unique ascites-derived PDAC primary cell culture model. This model has the potential to study signalling pathways in PDAC progression and to evaluate targeted therapies for the individual patient expeditiously, thereby supporting personalised treatment decisions.

Show MeSH
Related in: MedlinePlus