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A Proximal Culture Method to Study Paracrine Signaling Between Cells
Published on: August 28, 2018
Human myeloma cells adhere to fibronectin in response to hepatocyte growth factor
Randi Utne Holt1, Vadim Baykov, Torstein Baade Rø
1Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, MTFS, N-7489 Trondheim, Norway. randi.u.holt@medisin.ntnu.no
Background And Objectives:
Multiple myeloma is characterized by an accumulation of malignant plasma cells in the bone marrow. Inside the bone marrow, adhesion of myeloma cells to extracellular matrix proteins such as fibronectin may promote cell survival and induce drug resistance. In this work we examined the effect of hepatocyte growth factor (HGF) on the adhesion of myeloma cells and the signaling pathways involved.
Design And Methods:
Cell adhesion experiments were performed with the human myeloma cell line INA-6 and primary myeloma cells. The HGF signaling pathway was studied in INA-6 cells with the use of antibodies against VLA-4 integrin, and with inhibitors of various intracellular signaling molecules.
Results:
We found that HGF stimulated adhesion of myeloma cells to fibronectin. This event was dependent on the alpha4 and beta1 integrin subunits (VLA-4), but HGF did not increase the expression of integrins on the cell surface. Our findings suggest that HGF promotes myeloma cells to adhere via activation of the phosphatidylinositol 3-kinase (PI3K) pathway independently of AKT, but possibly through the involvement of nuclear factor kappa B (NF-kappaB). INA-6 cells adhered to fibronectin after stimulation by insulin-like growth factor or stromal cell-derived factor 1alpha, but this adhesion was less dependent on PI3K than HGF-mediated adhesion.
Interpretation And Conclusions:
his work points to HGF as a pro-adhesive factor in cell adherence to the bone marrow matrix protein fibronectin, an event known to promote cancer cell survival and drug resistance. Inhibiting HGF, its receptor c-Met or the VLA-4 integrin may be beneficial to the myeloma patient.
Insights
Hepatocyte growth factor (HGF) promotes multiple myeloma cell adhesion to fibronectin via the phosphatidylinositol 3-kinase (PI3K) pathway. This interaction highlights HGF as a therapeutic target for improving patient outcomes.
Area of Science:
- Oncology
- Cell Biology
- Molecular Signaling
Background:
- Multiple myeloma involves malignant plasma cell accumulation in bone marrow.
- Myeloma cell adhesion to fibronectin may enhance survival and drug resistance.
- Hepatocyte growth factor (HGF) role in myeloma cell adhesion and signaling was investigated.
Purpose of the Study:
- To examine the effect of HGF on myeloma cell adhesion to fibronectin.
- To elucidate the signaling pathways involved in HGF-mediated myeloma cell adhesion.
Main Methods:
- Cell adhesion assays using INA-6 myeloma cell line and primary myeloma cells.
- Investigation of HGF signaling pathway using VLA-4 integrin antibodies and pathway inhibitors.
- Analysis of phosphatidylinositol 3-kinase (PI3K) and nuclear factor kappa B (NF-kappaB) involvement.
Main Results:
- HGF significantly stimulated myeloma cell adhesion to fibronectin.
- Adhesion was dependent on VLA-4 integrin (alpha4 and beta1 subunits) but not increased integrin expression.
- HGF-induced adhesion involved PI3K pathway activation, potentially via NF-kappaB, independent of AKT.
Conclusions:
- HGF acts as a pro-adhesive factor for myeloma cells on fibronectin.
- This adhesion mechanism contributes to myeloma cell survival and drug resistance.
- Targeting HGF, c-Met, or VLA-4 integrin may offer therapeutic benefits for myeloma patients.
