The mRNA expression level for epidermal growth factor receptor (growth), basic fibroblast growth factor and interleukin-8 (angiogenesis), type IV collagenase (invasion), E-cadherin and carcinoembryonic antigen (adhesion), and the multidrug resistance gene mdr-1 (drug resistance) in the human KM12 colon carcinoma cell lines and clones with different metastatic potential was measured by Northern blot analysis and by in situ hybridization technique.
The close relationship between aneuploidy, EGF-R positive expression, node involvement, and tumor invasion suggests that these parameters may be indicators of high malignancy.
No consensus as to the involvement of the epidermal growth factor receptor (EGF-R) in colorectal carcinomas has yet been attained, although they are assumed to play a role in the metastasis to lymph nodes and recurrence of breast carcinoma and bladder carcinoma invasion.
Elevated levels of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) have been demonstrated in prostate cancer cell lines and clinical specimens suggesting a role for polypeptide growth factors in prostate tumor cell growth and invasion.
It is noteworthy that coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 was detected in 10 esophageal carcinomas (31.3%) and was significantly related to extramucosal tumor invasion (P = 0.02), whereas such a relationship was not shown by each sole expression.
The steady-state mRNA expression levels for epidermal growth factor receptor (EGFR; growth), basic fibroblast growth factor (bFGF) and interleukin (IL)-8 (angiogenesis), 72-kd and 92-kd type IV collagenase (invasion), E-cadherin (adhesion), and multidrug resistance (mdr-1; drug resistance) were measured by Northern blot and colorimetric in situ hybridization techniques in human PC-3M cells and selected cell variants with different metastatic potentials.
Up-regulated signaling from the epidermal growth factor receptor (EGFR) has been correlated with tumor invasion and metastasis in numerous human neoplasias.
The expression of epidermal growth factor receptor (growth), basic fibroblast growth factor [(bFGF), angiogenesis], type IV collagenase (invasion), E-cadherin (adhesion), and multidrug-resistant (mdr)-1 (drug resistance) mRNA was examined using an in situ mRNA hybridization (ISH) technique and Northern blot analysis.
Therefore, we investigated whether this PLCgamma signaling pathway also was rate-limiting for invasion in other tumor cell lines and types and whether this EGFR activity is subsumed by the closely related ErbB2.
In this study, we utilize carcinoma cells depleted of ErbB2, but not other ErbB receptor members, to specifically examine the role of ErbB2 in carcinoma cell migration and invasion.
A significant reduction of invasion in four selected EGFR-overexpressing cell lines was found with 30 nM ICR62 (from 50% to 70%; p < 0.001) but there was no effect in two cell lines with normal EGFR levels.
A specific anti-EGFR monoclonal antibody (mAb ICR62) inhibited MMP up-regulation, migration and invasion induced by all three ligands, whereas an anti-c-erbB-2 mAb ICR12 inhibited mitogenic and motogenic responses following ligand stimulation but had no effect on MMP expression.
Of the three tested breast cancer cell lines that exhibit low invasion capacity (BT-20, MCF-7, and T47D cells), erbB receptors were specifically affected by ethanol only in the T47D cells.
The ability of a specific inhibitor of EGF-R tyrosine kinase, ZM 252868, (TKI) to alter various parameters related to growth in DU145 and PC3 cell lines was investigated, by immunocytochemistry, Northern blotting, Western blotting and invasion assays.
Finally, we show that ERBB2-dependent medulloblastoma cell invasion in vitro and prometastatic gene expression in vivo can be blocked using the ERBB tyrosine kinase inhibitor OSI-774.
In four of these five cases, multiple regions of the tumor were available for examination; FISH demonstrated a gradation of EGFR amplification, with highly amplified cells, primarily at the invading edges rather than the relatively solid tumor centers, suggesting that EGFR overexpression, when selected for in vivo, may be related to tumor invasion.
We describe strategies to: i) target EGFR, its ligand-independent variant EGFRvIII, and PDGFR on the cell surface, ii) inhibit constitutively activate RAS/MAPK and PI3K/Akt signaling pathways, iii) target TP53 mutant tumors, and iv) block GBM angiogenesis and invasion.
Our results indicate that EGF is a potent stimulative agent for both growth and invasion in prostate cancer cells, and that targeting the EGFR function inhibits not only tumor growth but also invasiveness.