Topology impacts TRAIL therapy: Differences in primary cancer growth and liver metastasis between orthotopic and subcutaneous xenotransplants of pancreatic ductal adenocarcinoma cells.
Hepatobiliary Pancreat Dis Int
; 20(3): 279-284, 2021 Jun.
Article
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| MEDLINE
| ID: mdl-33947634
ABSTRACT
BACKGROUND:
To study novel treatment modalities for pancreatic ductal adenocarcinoma (PDAC), we need to transfer the knowledge from in vitro to in vivo. It is important to mirror the clinical characteristics of the typically local invasive growth of pancreatic cancer and the distant spread resulting in liver metastasis. Notably, for xenotransplant studies using human specimen, two models, i.e. subcutaneous (s.c.) and orthotopic (o.t.) transplantation are widely used.METHODS:
The subcutaneously and orthotopically inoculated Colo357 Bcl-xL cell-derived tumors were directly compared with and without TNF-related apoptosis inducing ligand (TRAIL) treatment. The size of primary tumors, number of liver metastasis and the histologic markers Ki67, M30, TNF-α and CD31 were assessed.RESULTS:
Upon TRAIL treatment, the primary tumors did not change their size, neither in the s.c. nor in the o.t. approaches. But when s.c. was compared to o.t., the size of the s.c. tumors was more than two-fold bigger than that of the o.t. tumors (P < 0.01). However, mice with orthotopically inoculated PDAC cells developed liver metastasis upon TRAIL treatment much more frequently (n = 13/17) than mice with subcutaneously inoculated PDAC cells (n = 1/11) (P < 0.01). As a likely driving force for this increased metastasis, a higher TNF-α staining intensity in the o.t. tumors was observed by immunohistochemistry.CONCLUSIONS:
These data from a direct side-by-side comparison underline the importance of the proper inoculation site of the PDAC cells. Local invasion and liver metastases are a hallmark of PDAC in the clinic; the o.t. model is clearly superior in reflecting this setting. Moreover, a serious side-effect of a possible new therapeutic compound became obvious only in the o.t.Palabras clave
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Carcinoma Ductal Pancreático
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Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Hepatobiliary Pancreat Dis Int
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2021
Tipo del documento:
Article