Alteration on the Expression of IL-1, PDGF, TGF-β, EGF, and FGF Receptors and c-Fos and c-Myc Proteins in Bone Marrow Mesenchymal Stroma Cells from Advanced Untreated Lung and Breast Cancer Patients

Abstract

Previously, we reported a deficient cloning capacity of the bone marrow (BM) mesenchymal stem cells to give colony-forming unit fibroblast (CFU-F) and an inefficient confluence capacity of BM stromal cells in advanced untreated lung cancer patients (LCP) and breast cancer patients (BCP). Moreover, a decreased level of bFGF at day 7 in the conditioned media from BM CFU-F cultures was found in both cancer groups when compared to the normal range. The current study was specially undertaken, to evaluate the percentage of subconfluent fibroblasts expressing receptors (R) of interleukin-1 (IL-1), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor (TGF-beta), epidermal growth factor (EGF), and the proteins c-Fos and c-Myc in BM primary cultures from untreated LCP and BCP. An immunocytochemical study on subconfluent BM fibroblast cultures from 13 healthy patients, 16 LCP, and 8 BCP was performed, using as primary antibodies, anti-type I of IL-1 R (IL-1R-1), anti-alpha, beta chains of PDGF R (PDGFR-alpha, PDGFR-beta), anti-type I of FGF R (FGFR-I), anti-type I, II, and III of TGF-beta R (TGF-betaR-I, TGF- betaR-II, and TGF-betaR-III), anti-EGF R, anti-c-Fos, and anti-c-Myc. A diminished percentage of subconfluent fibroblasts expressing PDGFR-alpha, TGFbetaR-I, II, III, EGFR, and FGFR-I was found in LCP and BCP compared to healthy patients. A diminished percentage of subconfluent fibroblasts expressing c-Fos and c-Myc was found in patients when compared to healthy patients. The alterations we describe could help to explain the deficiency regarding the proliferative and confluence capacity of BM stroma cells in cancer patients.

Fibronectin, Vitronectin, and Collagen I Induce Chemotaxis and Haptotaxis of Human and Rabbit Mesenchymal Stem Cells in a Standardized Transmembrane Assay

“…Nonetheless, studies with mesenchymal cells that bear the cognate receptors (46) have reported conflicting results concerning motogenic properties, some of which can be accounted for by the use of different species, as mentioned above, but also possibly due to a lack in standards in the procedures to assay cell migration (47,48). The in vitro transmembrane chemotaxis assay (TCA), also named the modified Boyden chamber assay, is the assay of choice for identifying pro-or anti-motogenic compounds (49).…”

Systematical Detection of Significant Genes in Microarray Data by Incorporating Gene Interaction Relationship in Biological Systems

“…In dataset2, mapping those uniquely selected genes by our method to cancer pathways left 12 genes, BID (GeneID: 637), CCNE2 (GeneID: 9134) [36], DVL3 (GeneID: 1857), FGF7 (GeneID: 2252), FGFR1 (GeneID: 2260), FGFR2 (GeneID: 2263), FZD4 (GeneID: 8322), MAP2K2 (GeneID: 5605), PDGFB (GeneID: 5155), PGF (GeneID: 5228) [37], PML (GeneID: 5371), and WNT1 (GeneID: 7471) ( Table S2 in File S5 ). Interestingly, we found that those genes, WNT1, FZD4, and DVL3 are enriched in the Wnt signaling pathway ( Figure S17 ) [38]–[41].…”

Regulation of Multilineage Gene Expression and Apoptosis during in vitro Expansion of Human Bone Marrow Stromal Cells with Different Cell Culture Media

“…Recent reports have shown that hBMSCs express receptors for PDGF and EGF and that proliferation can be stimulated by heparin-binding EGF-like growth factor (HB-EGF), which interacts with erbB4 and EGFR [Hofer et al, 2005;Krampera et al, 2005;Kratchmarova et al, 2005]. The receptors for EGF and PDGF are prototypical tyrosine kinase receptors present on most adherent cells, including MSCs [Ingram and Bonner, 2006], and are expressed on human MSCs as demonstrated by reported cellular responses [Hofer et al, 2005;Krampera et al, 2005]. Upon binding of EGF and PDGF, EGFR and PDGFR activate ERK (extracellular signal-regulated protein kinase), AKT (protein kinase B/akt) and PLC-␥ (phospholipase C-␥ ) which promote cell proliferation.…”

“…These results are also in line with those of Tamama et al [2006] who reported that EGFR ligands did not interfere with pluripotency of BMSCs or drive these cells into specific lineages. EGF and PDGF have been shown to inhibit collagen synthesis and alkaline phosphatase activity, and EGFR signaling was proposed as a negative regulator of osteogenic differentiation on BMSCs and preosteoblastic MC3T3 E1 cells [Chien et al, 2000;Gruber et al, 2004;Hofer et al, 2005]. The lack of significance in expression of Cbf-␣ 1 may be explained by the fact that the type I transcript of this transcription factor is also constitutively expressed in non-osseous mesenchymal tissues and plays a regulatory role in early stages of mesenchymal cell development [Banerjee et al, 2001].…”