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Journal of Experimental and Clinical Cancer Research

, 33:86

First Online: 30 September 2014Received: 02 September 2014Accepted: 25 September 2014DOI: 10.1186-s13046-014-0086-5

Cite this article as: Abdouh, M., Zhou, S., Arena, V. et al. J Exp Clin Cancer Res 2014 33: 86. doi:10.1186-s13046-014-0086-5

Abstract

BackgroundHuman cancer cells can transfer signaling molecules to neighboring and distant cells predisposing them to malignant transformation. This process might contribute to tumor progression and invasion through delivery of oncogenes or inhibitors of tumor suppressor genes, derived from the primary tumor cells, to susceptible target cells. The oncogenic potential of human cancer serum has been described in immortalized mouse fibroblasts but has not been shown yet in human cells. The objective of this study was to determine whether metastatic cancer patient sera have the ability to induce neoplastic transformation in immortalized human embryonic kidney HEK293 cells, human embryonic stem cells hESCs, human mesenchymal stem cells hMSCs and human adult liver fibroblasts hALFs.

MethodsEarly passage HEK293 cells, hESCs, hMSCs and hALFs were exposed to cancer patient serum, or cancer cells-derived condition medium for 3 weeks. Treated cells were analyzed for cell proliferation and transformation both in vitro and in vivo.

ResultsHEK293 cells exposed to cancer serum increased their proliferative capability and displayed characteristics of transformed cells, as evaluated by in vitro anchorage-independent growth assay and in vivo tumorigenesis in immunodeficient mice. The same phenotypes were acquired when these cells were cultured in cancer cell line conditioned medium suggesting that the putative oncogenic factors present in the serum might derive directly from the primary tumor. Histopathological analyses revealed that the tumors arising from cancer patient serum and conditioned medium-treated HEK293 cells were poorly differentiated and displayed a high proliferative index. In contrast, neither of these phenomena was observed in treated hMSCs and hALFs. Intriguingly enough, hESC-treated cells maintained their self-renewal and differentiation potentials, as shown by in vitro sphere formation assay and in vivo development of teratomas in immunodeficient mice.

ConclusionOur results indicate that cancer patients serum is able to induce oncogenic transformation of HEK293 cells and maintain the self-renewal of hESCs. To our knowledge, this is the first study that demonstrates the oncogenic transformation potential of cancer patient serum on human cells. In depth characterization of this process and the molecular pathways involved are needed to confirm its validity and determine its potential use in cancer therapy.

KeywordsHuman cancer serum Transformation Metastasis HEK293 Abbreviations7-AAD7-Amino Actinomycin D

ANOVAAnalysis of variance

BSABovine serum albumin

CFSECarboxyfluorescein succinimidyl ester

DABDiaminobenzidine

FBSFetal bovine serum

hALFsHuman adult liver fibroblast

HEK293Human embryonic kidney 293 cells

hESCsHuman embryonic stem cells

hMSCsHuman mesenchymal stem cells

PDLPopulation doubling level

Electronic supplementary materialThe online version of this article doi:10.1186-s13046-014-0086-5 contains supplementary material, which is available to authorized users.

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Author: Mohamed Abdouh - Shufeng Zhou - Vincenzo Arena - Manuel Arena - Anthoula Lazaris - Ronald Onerheim - Peter Metrakos - Goffr

Source: https://link.springer.com/



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