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2016 ; 35
(ä): 80
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Transfer of malignant trait to BRCA1 deficient human fibroblasts following
exposure to serum of cancer patients
#MMPMID27179759
Hamam D
; Abdouh M
; Gao ZH
; Arena V
; Arena M
; Arena GO
J Exp Clin Cancer Res
2016[May]; 35
(ä): 80
PMID27179759
show ga
BACKGROUND: It was reported that metastases might occur via transfer of
biologically active blood circulating molecules from the primary tumor to distant
organs rather than only migration of cancer cells. We showed in an earlier study
that exposure of immortalized human embryonic kidney cells (HEK 293) to cancer
patient sera, induce their transformation into undifferentiated cancers due to a
horizontal transfer of malignant traits. In the present work, we tested the
hypothesis that even other human cells as long as they are deficient for a single
oncosuppressor gene might undergo malignant transformation when exposed to human
cancer serum. METHODS: We used the CRISPR/Cas9 system to establish a stable BRCA1
knockout (KO) in human fibroblasts. The BRCA1-KO fibroblasts were exposed to
cancer patients' sera or healthy patients' sera for 2 weeks. Treated cells were
analyzed for cell proliferation and transformation to study their susceptibility
to the oncogenic potential of cancer patients' sera and to determine the possible
mechanisms underlying their hypothesized transformation. RESULTS: BRCA1-KO
fibroblasts treated with cancer patients' sera displayed higher proliferation and
underwent malignant transformation as opposed to wild type control fibroblasts,
which were not affected by exposure to cancer patients' sera. The malignant
transformation was not seen when BRCA1-KO fibroblasts were treated with healthy
human sera. Histological analysis of tumors generated by BRCA1-KO fibroblasts
showed that they were carcinomas with phenotypical characteristics related to the
cancers of the blood donor patients. Interestingly, BRCA1-KO fibroblasts were
significantly more prone to internalize serum-derived exosomes, when compared to
wild type fibroblasts. This suggests that oncosuppressor genes might protect the
integrity of the cell genome also by blocking integration of cancer-derived
exosomes. CONCLUSION: These data support the hypothesis that any human cells
carrying a single oncosuppressor mutation is capable of integrating cancer
factors carried in the blood and undergo complete malignant transformation.
Oncosuppressor genes might protect the cell genome by impeding the integration
inside the cells of these mutating factors.