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Characterization of novel carcinoma cell lines for the analysis of therapeutical strategies fighting pancreatic cancer.

Zechner D, Bürtin F, Amme J, Lindner T, Radecke T, Hadlich S, Kühn JP, Vollmar B - Cell Biosci (2015)

Bottom Line: In tissue culture 6606PDA and 6606l proliferated faster than 7265PDA. 7265PDA cells were, however, significantly more sensitive to gemcitabine as assessed by BrdU-incorporation and trypan blue exclusion assays in vitro.All three cell lines can be used in vitro for testing combinatorial therapies with gemcitabine.Diffusion-weighted MRI proved to be an appropriate method to predict tumor remission.

View Article: PubMed Central - PubMed

Affiliation: Institute for Experimental Surgery, Rostock University Medical Center, University of Rostock, Schillingallee 69a, 18057 Rostock, Germany.

ABSTRACT

Background: Preclinical evaluations of chemotherapies depend on clinically relevant animal models for pancreatic cancer. The injection of syngeneic murine adenocarcinoma cells is one efficient option to generate carcinomas in mice with an intact immune system. However, this option is constrained by the paucity of appropriate cell lines.

Results: The murine pancreatic adenocarcinoma cell lines 6606PDA and 7265PDA were compared to the 6606l cell line isolated from a liver metastasis from mice suffering from pancreatic cancer. In tissue culture 6606PDA and 6606l proliferated faster than 7265PDA. 7265PDA cells were, however, significantly more sensitive to gemcitabine as assessed by BrdU-incorporation and trypan blue exclusion assays in vitro. Within 1 week after injection of either one of these three cell lines into the pancreas of C57BL/6J mice, carcinomas were observed by T2 weighted magnetic resonance imaging and histology. Three weeks after injecting 6606PDA or 6606l cells large carcinomas could be characterized, which were surrounded by extensive desmoplastic reaction. After injection of 7265PDA cells, however, remission of cancer was observed between the first and the third week. Compared to 6606PDA cell derived carcinomas a higher apparent diffusion coefficient was quantified by diffusion weighted magnetic resonance imaging in these tumors. This correlated with reduced cancer cell density observed on histological sections.

Conclusion: All three cell lines can be used in vitro for testing combinatorial therapies with gemcitabine. The 6606PDA and 6606l cell lines but not the 7265PDA cell line can be used for evaluating distinct therapies in a syngeneic carcinoma model using C57BL/6J mice. Diffusion-weighted MRI proved to be an appropriate method to predict tumor remission.

No MeSH data available.


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Characterization of carcinomas by diffusion-weighted MRI and histology during the early phase of tumor growth. a Characteristic diffusion-weighted MRI of 6606PDA and 7265PDA cell derived carcinomas (day 5/6). b Quantification of water diffusion of 6606PDA and 7265PDA cell derived carcinomas by diffusion-weighted MRI, as given by the ADC value. c characteristic haematoxylin/eosin (H/E) staining of histological sections of carcinomas during the early phase of tumor growth (dotted arrow pancreatic acinar cells, arrow cancer cells, arrowhead oedema with infiltrating inflammatory cells). A significant difference between indicated cohorts (*P = 0.01) is shown in the box plot (number of tumors analyzed: n = 4 for 6606PDA, n = 6 for 7265PDA; 2 independent experiments). Bar 100 μm
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Fig6: Characterization of carcinomas by diffusion-weighted MRI and histology during the early phase of tumor growth. a Characteristic diffusion-weighted MRI of 6606PDA and 7265PDA cell derived carcinomas (day 5/6). b Quantification of water diffusion of 6606PDA and 7265PDA cell derived carcinomas by diffusion-weighted MRI, as given by the ADC value. c characteristic haematoxylin/eosin (H/E) staining of histological sections of carcinomas during the early phase of tumor growth (dotted arrow pancreatic acinar cells, arrow cancer cells, arrowhead oedema with infiltrating inflammatory cells). A significant difference between indicated cohorts (*P = 0.01) is shown in the box plot (number of tumors analyzed: n = 4 for 6606PDA, n = 6 for 7265PDA; 2 independent experiments). Bar 100 μm

Mentions: To characterize differences between carcinomas derived from 6606PDA cells and 7265PDA diffusion-weighted MRI was performed during the early phase of tumor growth (Fig. 6a). Interestingly the calculated apparent diffusion coefficient (ADC), measured at the edge of both classes of carcinomas, was higher in carcinomas derived from 7265PDA cells than in carcinomas derived from 6606PDA cells (Fig. 6b). This observation correlated well with the histology of these tumors. 6606PDA cell derived carcinomas were characterized by many densely packed cancer cells (Fig. 6c upper panel). Inflammatory cells surrounded these carcinomas, but only few inflammatory cells were observed within these carcinomas (Fig. 6c upper panel). 7265PDA cell derived carcinomas were characterized by oedema, massive infiltration of inflammatory cells, and few loosely packed cancer cells (Fig. 6c lower panel). These data suggest that less than a week after injection of 7265PDA cells the immune system of C57BL/6J mice prevented the accumulation of densely packed cancer cells. Instead, infiltrating inflammatory cells lead to a local oedema which results in a higher ADC value when diffusion-weighted MRI was performed.Fig. 6


Characterization of novel carcinoma cell lines for the analysis of therapeutical strategies fighting pancreatic cancer.

Zechner D, Bürtin F, Amme J, Lindner T, Radecke T, Hadlich S, Kühn JP, Vollmar B - Cell Biosci (2015)

Characterization of carcinomas by diffusion-weighted MRI and histology during the early phase of tumor growth. a Characteristic diffusion-weighted MRI of 6606PDA and 7265PDA cell derived carcinomas (day 5/6). b Quantification of water diffusion of 6606PDA and 7265PDA cell derived carcinomas by diffusion-weighted MRI, as given by the ADC value. c characteristic haematoxylin/eosin (H/E) staining of histological sections of carcinomas during the early phase of tumor growth (dotted arrow pancreatic acinar cells, arrow cancer cells, arrowhead oedema with infiltrating inflammatory cells). A significant difference between indicated cohorts (*P = 0.01) is shown in the box plot (number of tumors analyzed: n = 4 for 6606PDA, n = 6 for 7265PDA; 2 independent experiments). Bar 100 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4551666&req=5

Fig6: Characterization of carcinomas by diffusion-weighted MRI and histology during the early phase of tumor growth. a Characteristic diffusion-weighted MRI of 6606PDA and 7265PDA cell derived carcinomas (day 5/6). b Quantification of water diffusion of 6606PDA and 7265PDA cell derived carcinomas by diffusion-weighted MRI, as given by the ADC value. c characteristic haematoxylin/eosin (H/E) staining of histological sections of carcinomas during the early phase of tumor growth (dotted arrow pancreatic acinar cells, arrow cancer cells, arrowhead oedema with infiltrating inflammatory cells). A significant difference between indicated cohorts (*P = 0.01) is shown in the box plot (number of tumors analyzed: n = 4 for 6606PDA, n = 6 for 7265PDA; 2 independent experiments). Bar 100 μm
Mentions: To characterize differences between carcinomas derived from 6606PDA cells and 7265PDA diffusion-weighted MRI was performed during the early phase of tumor growth (Fig. 6a). Interestingly the calculated apparent diffusion coefficient (ADC), measured at the edge of both classes of carcinomas, was higher in carcinomas derived from 7265PDA cells than in carcinomas derived from 6606PDA cells (Fig. 6b). This observation correlated well with the histology of these tumors. 6606PDA cell derived carcinomas were characterized by many densely packed cancer cells (Fig. 6c upper panel). Inflammatory cells surrounded these carcinomas, but only few inflammatory cells were observed within these carcinomas (Fig. 6c upper panel). 7265PDA cell derived carcinomas were characterized by oedema, massive infiltration of inflammatory cells, and few loosely packed cancer cells (Fig. 6c lower panel). These data suggest that less than a week after injection of 7265PDA cells the immune system of C57BL/6J mice prevented the accumulation of densely packed cancer cells. Instead, infiltrating inflammatory cells lead to a local oedema which results in a higher ADC value when diffusion-weighted MRI was performed.Fig. 6

Bottom Line: In tissue culture 6606PDA and 6606l proliferated faster than 7265PDA. 7265PDA cells were, however, significantly more sensitive to gemcitabine as assessed by BrdU-incorporation and trypan blue exclusion assays in vitro.All three cell lines can be used in vitro for testing combinatorial therapies with gemcitabine.Diffusion-weighted MRI proved to be an appropriate method to predict tumor remission.

View Article: PubMed Central - PubMed

Affiliation: Institute for Experimental Surgery, Rostock University Medical Center, University of Rostock, Schillingallee 69a, 18057 Rostock, Germany.

ABSTRACT

Background: Preclinical evaluations of chemotherapies depend on clinically relevant animal models for pancreatic cancer. The injection of syngeneic murine adenocarcinoma cells is one efficient option to generate carcinomas in mice with an intact immune system. However, this option is constrained by the paucity of appropriate cell lines.

Results: The murine pancreatic adenocarcinoma cell lines 6606PDA and 7265PDA were compared to the 6606l cell line isolated from a liver metastasis from mice suffering from pancreatic cancer. In tissue culture 6606PDA and 6606l proliferated faster than 7265PDA. 7265PDA cells were, however, significantly more sensitive to gemcitabine as assessed by BrdU-incorporation and trypan blue exclusion assays in vitro. Within 1 week after injection of either one of these three cell lines into the pancreas of C57BL/6J mice, carcinomas were observed by T2 weighted magnetic resonance imaging and histology. Three weeks after injecting 6606PDA or 6606l cells large carcinomas could be characterized, which were surrounded by extensive desmoplastic reaction. After injection of 7265PDA cells, however, remission of cancer was observed between the first and the third week. Compared to 6606PDA cell derived carcinomas a higher apparent diffusion coefficient was quantified by diffusion weighted magnetic resonance imaging in these tumors. This correlated with reduced cancer cell density observed on histological sections.

Conclusion: All three cell lines can be used in vitro for testing combinatorial therapies with gemcitabine. The 6606PDA and 6606l cell lines but not the 7265PDA cell line can be used for evaluating distinct therapies in a syngeneic carcinoma model using C57BL/6J mice. Diffusion-weighted MRI proved to be an appropriate method to predict tumor remission.

No MeSH data available.


Related in: MedlinePlus