Cancer-associated fibroblasts stimulate primary tumor growth and metastatic spread in an orthotopic prostate cancer xenograft model.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 07 2020
28 07 2020
Historique:
received:
12
04
2020
accepted:
03
07
2020
entrez:
30
7
2020
pubmed:
30
7
2020
medline:
15
12
2020
Statut:
epublish
Résumé
The unique microenvironment of the prostate plays a crucial role in the development and progression of prostate cancer (PCa). We examined the effects of cancer-associated fibroblasts (CAFs) on PCa progression using patient-derived fibroblast primary cultures in a representative orthotopic xenograft model. Primary cultures of CAFs, non-cancer-associated fibroblasts (NCAFs) and benign prostate hyperplasia-associated fibroblasts (BPHFs) were generated from patient-derived tissue specimens. These fibroblasts were coinjected together with cancer cells (LuCaP136 spheroids or LNCaP cells) in orthotopic PCa xenografts to investigate their effects on local and systemic tumor progression. Primary tumor growth as well as metastatic spread to lymph nodes and lungs were significantly stimulated by CAF coinjection in LuCaP136 xenografts. When NCAFs or BPHFs were coinjected, tumor progression was similar to injection of tumor cells alone. In LNCaP xenografts, all three fibroblast types significantly stimulated primary tumor progression compared to injection of LNCaP cells alone. CAF coinjection further increased the frequency of lymph node and lung metastases. This is the first study using an orthotopic spheroid culture xenograft model to demonstrate a stimulatory effect of patient-derived CAFs on PCa progression. The established experimental setup will provide a valuable tool to further unravel the interacting mechanisms between PCa cells and their microenvironment.
Identifiants
pubmed: 32724081
doi: 10.1038/s41598-020-69424-x
pii: 10.1038/s41598-020-69424-x
pmc: PMC7387494
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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