title: Transfer of malignant trait to immortalized human cells following exposure to human cancer serum.
abstract: BACKGROUND
  Human 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).
  
  
  METHODS
  Early 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.
  
  
  RESULTS
  HEK293 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Surgical Research Laboratories, McGill University, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, H3A 1A1, Canada. abdouhm2009@gmail.com.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdouh
authors.affiliation: Surgical Research Laboratories, McGill University, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, H3A 1A1, Canada. fenghesclab4@gmail.com.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Deparment of Obstetrics and Gynecology, Santo Bambino Hospital, via Torre del Vescovo 4, Catania, Italy. vincenzoarena@live.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Arena
authors.affiliation: Deparment of Surgical Sciences, Organ Transplantation and Advances Technologies, University of Catania, via Santa Sofia 84, Catania, Italy. manuelarena@live.it.
authors.forename: Manuel
authors.initials: M
authors.lastname: Arena
authors.affiliation: Surgical Research Laboratories, McGill University, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, H3A 1A1, Canada. anthoula.lazaris@mail.mcgill.ca.
authors.forename: Anthoula
authors.initials: A
authors.lastname: Lazaris
authors.affiliation: Department of Pathology, McGill University, St. Mary's Hospital, 3830 Lacombe Avenue, Montreal, H3T 1 M5, Canada. ronald.onerheim@mcgill.ca.
authors.forename: Ronald
authors.initials: R
authors.lastname: Onerheim
authors.affiliation: Surgical Research Laboratories, McGill University, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, H3A 1A1, Canada. peter.metrakos@mcgill.ca.|McGill University Health Center Multi-Organ, Transplant Program and Hepatopancreatobiliary Surgery, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, H3A 1A1, Canada. peter.metrakos@mcgill.ca.
authors.forename: Peter
authors.initials: P
authors.lastname: Metrakos
authors.affiliation: Surgical Research Laboratories, McGill University, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, H3A 1A1, Canada. goffredo.arena@mcgill.ca.|Department of Surgery, McGill University, St. Mary Hospital, 3830 Lacombe Avenue, Montreal, H3T 1 M5, Canada. goffredo.arena@mcgill.ca.
authors.forename: Goffredo Orazio
authors.initials: GO
authors.lastname: Arena
mesh_terms: D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood* / Q000473:pathology; D010641:Phenotype; D044967:Serum / Q000378:metabolism*; D013997:Time Factors; D047368:Tumor Burden
chemical_list: D017077:Culture Media, Conditioned