Exploitation of receptor tyrosine kinases by viral-encoded growth factors

2018 ◽  
Vol 36 (3-4) ◽  
pp. 118-140 ◽  
Author(s):  
Zabeen Lateef ◽  
Lyn M. Wise
Keyword(s):  
Growth Factors ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases

Receptor tyrosine kinases and growth factors expression in tumor thrombus cells in patients with renal cell carcinoma (RCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17073-e17073
Author(s):  
Maria Volkova ◽  
Ilya Tsimafeyeu ◽  
Dmitry Khochenkov ◽  
Anna Olshanskaia ◽  
Niko Vashakmadze ◽  
...  
Keyword(s):  
Growth Factors ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Tyrosine Kinases ◽  
Tumor Thrombus ◽  
Receptor Tyrosine Kinases ◽  
Detection System ◽  
Biological Significance ◽  
Expression Levels ◽  
Lower Expression

e17073 Background: To our knowledge, this is a first study describing the expression of the receptor tyrosine kinases (RTKs) and growth factors (GFs) in venous tumor thrombus cells and comparing results with the expression in primary RCC. Methods: Formalin-fixed paraffin-embedded specimens of tumor thrombus and primary tumor removed from 25 untreated pT3a-T4N0-1M0-1 RCC patients were evaluated by immunohistochemistry with primary antibodies to VEGF-A, FGF2, VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRα, and PDGFRβ (Abcam/Santa Cruz Biotech) and REAL™ EnVision™ Detection System (Agilent). The extent of expression was compared with 25 specimens of primary tumor tissue (selected from the same patients). Significant differences in the expression among these groups were assessed by chi-squared and Fisher's exact tests using a semi-quantitative method (H-score). The analysis of the correlation between expression levels and RCC characteristics was also performed. Results: Mean age was 62.0 (35-74) years. pT3a, pT3b, pT3c and pT4 stages were detected in 4 (16.0%), 13 (52.0%), 7 (28.0%), and 1 (4.0%) patients. Lymph node metastases were found in 9 (36.0%) cases, 15 (60.0%) patients had 1 or more metastatic sites. All RTKs and GFs were heavily expressed in primary tumor cells. Tumor thrombus cells were characterized by significant lower expression levels of VEGFR1, VEGFR2, and PDGFRα (p < 0.05 for all). Tendency to lower expression of VEGF-A (p = 0.06), FGF-2 (p = 0.046), FGFR1 (p = 0.077), and FGFR2 (p = 0.09) was observed in tumor thrombus cells (Table). VEGFR2 expression levels were 2-times reduced in patients with supradiaphragmatic thrombus (H-score = 21.4±12.0) compared to infradiaphragmatic thrombus (H-score = 55.0±8.5, p = 0.042). Furman grade correlated with the expression levels of VEGFR1 (p = 0.035) and FGFR1 (p = 0.022) in primary tumor cells; tumor invasion into venous wall correlated with the expression levels of VEGFR1 (p = 0.023) and FGFR2 (p = 0.005) in thrombus cells. Conclusions: RCC invasion into veins is accompanied by a decrease in expression of RTKs and GFs. Further studies are needed to understand the biological significance. [Table: see text]

scholarly journals Cd44 Enhances Neuregulin Signaling by Schwann Cells

2000 ◽  
Vol 150 (5) ◽  
pp. 1071-1084 ◽  
Author(s):  
Larry S. Sherman ◽  
Tilat A. Rizvi ◽  
Saikumar Karyala ◽  
Nancy Ratner
Keyword(s):  
Growth Factors ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Cd44 Expression ◽  
High Affinity ◽  
Transmembrane Glycoprotein ◽  
Low Expression

We describe a key role for the CD44 transmembrane glycoprotein in Schwann cell–neuron interactions. CD44 proteins have been implicated in cell adhesion and in the presentation of growth factors to high affinity receptors. We observed high CD44 expression in early rat neonatal nerves at times when Schwann cells proliferate but low expression in adult nerves, where CD44 was found in some nonmyelinating Schwann cells and to varying extents in some myelinating fibers. CD44 constitutively associated with erbB2 and erbB3, receptor tyrosine kinases that heterodimerize and signal in Schwann cells in response to neuregulins. Moreover, CD44 significantly enhanced neuregulin-induced erbB2 phosphorylation and erbB2–erbB3 heterodimerization. Reduction of CD44 expression in vitro resulted in loss of Schwann cell–neurite adhesion and Schwann cell apoptosis. CD44 is therefore crucial for maintaining neuron–Schwann cell interactions at least partly by facilitating neuregulin-induced erbB2–erbB3 activation.

scholarly journals Intracellular control of developmental and regenerative axon growth

2006 ◽  
Vol 361 (1473) ◽  
pp. 1575-1592 ◽  
Author(s):  
Feng-Quan Zhou ◽  
William D Snider
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Glycogen Synthase ◽  
Axon Growth ◽  
Protein Translation ◽  
Activated T Cells ◽  
Local Assembly ◽  
Gsk 3Β

Axon growth is a highly regulated process that requires stimulating signals from extracellular factors. The extracellular signals are then transduced to regulate coordinately gene expression and local axon assembly. Growth factors, especially neurotrophins that act via receptor tyrosine kinases, have been heavily studied as extracellular factors that stimulate axon growth. Downstream of receptor tyrosine kinases, recent studies have suggested that phosphatidylinositol-3 kinase (PI3K) regulates local assembly of axonal cytoskeleton, especially microtubules, via glycogen synthase kinase 3β (GSK-3β) and multiple microtubule binding proteins. The role of extracellular signal regulated kinase (ERK) signalling in regulation of local axon assembly is less clear, but may involve the regulation of local protein translation. Gene expression during axon growth is regulated by transcription factors, among which cyclic AMP response element binding protein and nuclear factors of activated T-cells (NFATs) are known to be required for neurotrophin (NT)-induced axon extension. In addition to growth factors, extracellular matrix molecules and neuronal activity contribute importantly to control axon growth. Increasingly, evidence suggests that these influences act to enhance growth via coordinating with growth factor signalling. Finally, evidence is emerging that developmental versus regenerative axon growth may be mediated by distinct signalling pathways, both at the level of gene transcription and at the level of local axon assembly.

Growth factors and associated signalling pathways in tumour progression and in cancer treatment

2019 ◽  
pp. 105-122
Author(s):  
Nadège Gaborit ◽  
Yosef Yarden
Keyword(s):  
Growth Factors ◽  
Tyrosine Kinases ◽  
Normal Tissue ◽  
Receptor Tyrosine Kinases ◽  
Tumour Progression ◽  
Signalling Pathways ◽  
Polypeptide Growth Factors ◽  
Growth Factor Signalling ◽  
Approved Drugs ◽  
Nuclear Alterations

To gain increased proliferation, blood supply, invasiveness, and resistance to cytotoxic treatments, cancer cells continuously secrete polypeptide growth factors, or they utilize factors produced by the associated normal tissue and the immunological microenvironment. The growth factors relay biochemical messages by binding with receptor tyrosine kinases (RTKs) located at the cell surface. In response to activation and receptor auto-phosphorylation, RTKs mobilize diverse signalling pathways, which culminate in cytoplasmic and nuclear alterations, including activation of gene expression programmes. This chapter describes several well-characterized growth factors, highlights the cognate receptors and downstream signalling pathways, and exemplifies involvement of specific growth factors in maintenance of the hallmarks of cancer. An account of clinically approved drugs able to intercept growth factor signalling closes this chapter.

Growth factors and associated signalling pathways in tumour progression and in cancer treatment

2019 ◽  
pp. 105-122
Author(s):  
Nadège Gaborit ◽  
Yosef Yarden
Keyword(s):  
Growth Factors ◽  
Tyrosine Kinases ◽  
Normal Tissue ◽  
Receptor Tyrosine Kinases ◽  
Tumour Progression ◽  
Signalling Pathways ◽  
Polypeptide Growth Factors ◽  
Growth Factor Signalling ◽  
Approved Drugs ◽  
Nuclear Alterations

To gain increased proliferation, blood supply, invasiveness, and resistance to cytotoxic treatments, cancer cells continuously secrete polypeptide growth factors, or they utilize factors produced by the associated normal tissue and the immunological microenvironment. The growth factors relay biochemical messages by binding with receptor tyrosine kinases (RTKs) located at the cell surface. In response to activation and receptor auto-phosphorylation, RTKs mobilize diverse signalling pathways, which culminate in cytoplasmic and nuclear alterations, including activation of gene expression programmes. This chapter describes several well-characterized growth factors, highlights the cognate receptors and downstream signalling pathways, and exemplifies involvement of specific growth factors in maintenance of the hallmarks of cancer. An account of clinically approved drugs able to intercept growth factor signalling closes this chapter.

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