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Open AccessReview

Hepatocyte Growth Factor: A Microenvironmental Resource for Leukemic Cell Growth

Stem Cell Laboratory, Department of Experimental Medicine, University of Genoa, V. Pastore 3, 16132 Genova, Italy
Molecular Pathology Unit, IRCCS Polyclinic Hospital San Martino, L.go R. Benzi n.10, 16132 Genova, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(2), 292;
Received: 25 October 2018 / Revised: 7 January 2019 / Accepted: 9 January 2019 / Published: 12 January 2019
(This article belongs to the Special Issue Hepatocyte Growth Factor (HGF))
Chronic lymphocytic leukemia (CLL) is characterized by the progressive expansion of B lymphocytes CD5+/CD23+ in peripheral blood, lymph-nodes, and bone marrow. The pivotal role played by the microenvironment in disease pathogenesis has become increasingly clear. We demonstrated that bone marrow stromal cells and trabecular bone cells sustain survival of leukemic B cells through the production of hepatocyte growth factor (HGF). Indeed the trans-membrane kinase receptor for HGF, c-MET, is expressed on CLL cells and STAT3 TYR705 or AKT phosphorylation is induced after HGF/c-MET interaction. We have further observed that c-MET is also highly expressed in a peculiar type of cells of the CLL-microenvironment showing nurturing features for the leukemic clone (nurse-like cells: NLCs). Since HGF treatment drives monocytes toward the M2 phenotype and NLCs exhibit features of tumor associated macrophages of type 2 we suggested that HGF, released either by cells of the microenvironment or leukemic cells, exerts a double effect: i) enhances CLL cells survival and ii) drives differentiation of monocytes-macrophages to an oriented immune suppressive phenotype. We here discuss how paracrine, but also autocrine production of HGF by malignant cells, may favor leukemic clone expansion and resistance to conventional drug treatments in CLL, as well as in other hematological malignancies. Novel therapeutic approaches aimed to block HGF/c-MET interactions are further proposed. View Full-Text
Keywords: HGF; c-MET; hematological neoplasia; microenvironment HGF; c-MET; hematological neoplasia; microenvironment
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MDPI and ACS Style

Giannoni, P.; Fais, F.; Cutrona, G.; Totero, D.d. Hepatocyte Growth Factor: A Microenvironmental Resource for Leukemic Cell Growth. Int. J. Mol. Sci. 2019, 20, 292.

AMA Style

Giannoni P, Fais F, Cutrona G, Totero Dd. Hepatocyte Growth Factor: A Microenvironmental Resource for Leukemic Cell Growth. International Journal of Molecular Sciences. 2019; 20(2):292.

Chicago/Turabian Style

Giannoni, Paolo; Fais, Franco; Cutrona, Giovanna; Totero, Daniela d. 2019. "Hepatocyte Growth Factor: A Microenvironmental Resource for Leukemic Cell Growth" Int. J. Mol. Sci. 20, no. 2: 292.

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