Stem cell recruitment and liver de-differentiation in MMTV-neu (ErbB-2) transgenic mice.
The liver of tumor-bearing hosts manifests fetal phenotypes. We investigated the expression of differentiation markers on the liver in MMTV-neu (ErbB-2) transgenic mice, in the period from incipient neoangiogenesis to lung metastatization. We report AFP expression by hepatocytes in all lobular zones, CD34 cell arrest and subsequent hemopoiesis in periportal and mid-zone areas, oval-like cells (CD34+, CK19+, AFP+) and ductular reaction in portal tracts, portal CK19+ and GGT+ hepatoblast-like cells, and midzonal large dysplastic hepatocytes. We hypothesize that CD34 cells are recruited by the tumor from the marrow for angiogenic purposes and that their differentiation in the liver is influenced by altered liver microenvironment(s). AFP may act as a growth factor and biological response modifier for these cells and for the tumor. Dysplasia might be enhanced by metabolic stress. We conclude that the liver differentiation potential is lobular-zone-dependent and that the risk for eventually developing a pre-malignant lesion is not negligible.
Freitas
Isabel
I
Department of Animal Biology, CNR Institute of Molecular Genetics, Session of Histochemistry and Cytometry, University of Pavia, Italy. freitas@unipv.it
Fracchiolla
Simona
S
Baronzio
Gianfranco
G
Griffini
Patrizia
P
Bertone
Roberta
R
Sitar
Gian Maria
GM
Barni
Sergio
S
Gerzeli
Giuseppe
G
Sacco
Maria Grazia
MG
D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology* / Q000821:virology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D007633:Keratins / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000235:genetics / Q000473:pathology* / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000509:alpha-Fetoproteins / Q000096:biosynthesis; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000509:alpha-Fetoproteins; D007633:Keratins; D005723:gamma-Glutamyltransferase