Transforming Growth Factor-α and Epidermal Growth Factor
Jason Kelley in Cytokines of the Lung, 2022
Epidermal growth factor, TGF-α, and HB-EGF are capable of inducing a wide variety of biological responses, both in vivo and in vitro, through activation of the EGF receptor. Many of these biological activities have been recently reviewed (Carpenter and Wahl, 1990) and, therefore, I will focus upon some of the qualitative and quantitative differences in activity that distinguish these growth factors. Both EGF and TGF-α stimulate the proliferation of cultured epithelial, endothelial, and mesenchymal cells. Curiously, they induce chemotaxis of epithelial and endothelial cells, but not of fibroblasts (Blay and Brown, 1985; Bade and Feindler, 1988; Grotendorst et al., 1989; Mawatari et al., 1991). In contrast, HB-EGF is mitogenic for epithelial and mesenchymal cells, but not for endothelial cells in vitro (Hagashiyama, 1991). The reason for these differences is not readily apparent, since all three of these cell types express the EGF receptor. Furthermore, it is important to emphasize that these qualitative differences have been demonstrated only in cultured cells. If, however, these differences also occur in vivo, then the target cell responses elicited in a given tissue would be highly dependent on which of these growth factors is present.
Carcinogenesis Studies In Human Gastrointestinal Epithelium
Herman Autrup, Gary M. Williams in Experimental Colon Carcinogenesis, 2019
Cell cultures of benign colonic tumors have been described by Friedman et al.23 Adenomatous colonic tissue was obtained by endoscopy. The tissue was minced and treated with collagenase IV and neuramindase V until it was dispersed into small fragments. The segments were cultured in Medium 199 supplemented with 15% heat-inactivated fetal calf serum, hydrocortisone (1 ¼g/ml), EGF (50 ¼g/ml), cholera toxin (10−11M), insulin (0.1 unit/ml), transferrin (17 ¼g/ml), ascorbic acid (38 ¼g/ml), folic acid (2 ¼g/ml), dextrose (5 mg/ml), 4-(2-hydroxyethyl)-l-piperazine-ethanesulfonic acid (25 mM) (pH 7.3), and H2SeO3 (10−7M). Epithelial outgrowths or colony formation were established from groups of epithelial cells, but not by single cells. A better attachment of tissue pieces was obtained when the fragments were seeded onto nonadherent substrate such as polycarbonate filters or onto collagen-coated dishes. Epithelial cells grown from adenomatous tissue are shown in Figure 5. Epidermal growth factor affected the replication of epithelial cells from different types of benign tumors differently. The greatest stimulation was observed in cells from tubular adenoma, the type least prone to malignancy, while villotubular and villous adenomas were not mitogenically stimulated by EGF.
Inhibition of Growth Factor Action as an Approach to Cancer Chemotherapy
Robert I. Glazer in Developments in Cancer Chemotherapy, 2019
The use of inhibitors of growth factor action as antineoplastic agents is in its infancy. Many crucial questions remain to be answered before this approach will be on a truly rational basis. Which growth factors (if any) exert a controlling influence on a specific type of tumor? This question is critical in determining the effectiveness of a particular inhibitor on a particular tumor. In some cases the requirement for growth factors may be bypassed completely rather than merely reduced or satisfied by autocrine secretion of growth factors. In these instances the use of growth factor inhibitors would be ineffective. What are the roles of these factors in normal cell function? This question is critical in determining the toxicity of any inhibitor of growth factor action. Two of the best known growth factors, EGF and PDGF, may play essential roles in development and wound healing, respectively. A knowledge of the role of these growth factors in normal physiology is essential for an understanding of any selective effects against transformed cells.
Successful production of human epidermal growth factor in tobacco chloroplasts in a biologically active conformation
Published in Growth Factors, 2023
Yunpeng Wang, Jieying Fan, Niaz Ahmad, Wen Xin, Zhengyi Wei, Shaochen Xing
Epidermal growth factor (EGF) can promote the proliferation and differentiation of epidermal cells and regulate cell proliferation in the processes of embryo development, wound healing and tumorigenesis (Nanba et al. 2013). Due to its epidermal cell proliferation potential, EGF is widely used in the treatment of many kinds of wounds (Berlanga et al. 2013). However, EGF is a small peptide, and due to its small size (6.2 kDa), it can easily diffuse out from the administration site and may also run off from the serum (Kim et al. 2016). Moreover, EGF is quickly degraded in the chronic wounds and burned sites due to the high proteinase environment (Kong and Mooney 2007). Therefore, the successful treatment of wounds requires EGF in high quantity and multiple doses, which raises its demands not only in the pharmaceutical industry but also in the cosmetic industry (Kim et al. 2009).
Design and synthesis of novel quinazolinone-based derivatives as EGFR inhibitors with antitumor activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Amr Sonousi, Rasha A. Hassan, Eman O. Osman, Amr M. Abdou, Soha H. Emam
Molecular targeting therapy approach, that targets a crucial cancer-related enzyme or receptor, increases the tumour specificity and decreases the side effects3–5. The epidermal growth factor receptor (EGFR) is mainly involved in the growth factor signalling. Abnormal signalling and overexpression of this receptor enhance downstream effects such as cell survival, cell proliferation and angiogenesis which lead to uncontrolled cell proliferation and metastasis, which ultimately promote tumour growth (Figure 1)6. The EGFR is one of the members of ErbB tyrosine kinase receptors family7, and consists of two domains; an extracellular receptor domain connected via a transmembrane region to an intracellular domain with tyrosine kinase function8. Inhibition of EGFR by tyrosine kinase inhibitors (TKIs) delays these downstream effects and lead to inhibition of tumour growth. Many breast cancers express 2 × 106 EGFR molecules per cell which is more than 20-fold the expression of EGFR in normal cells9,10. This overexpression of EGFR in breast cancer as well as other cancer cells including colon and lung cancers made this a potential molecular target for inhibition11–14.
The effectiveness of cetuximab and panitumumab when combined with FOLFIRI in second-line treatment of KRAS wild type metastatic colorectal cancers. Single centre experience
Published in Journal of Chemotherapy, 2021
Pınar Gürsoy, Burcu Çakar, Elvina Almuradova, Murat Karateke, Başak Doğanavşargil, Murat Sezak, Mustafa Harman, Bülent Karabulut
Epidermal growth factor (EGF) plays an important role in tumour growth and proliferation in CRC. When the epidermal growth factor ligand binds to the EGF receptor, intracellular RAS-RAF-MEK-ERK and the PI3-AKT-m TOR signalling pathways are activated.10 Cetuximab and panitumumab are monoclonal antibodies that act by inhibiting these pathways and target the extracellular domain III of EGFR. Both are commonly used in combination with chemotherapy in K-ras wild type disease.11 Cetuximab is a chimeric immunoglobulin G1 antibody, while panitumumab is a human immunoglobulin G2 antibody.11,12 Although the mechanism of action of panitumumab and cetuximab is the same, their main difference is that the panitumumab has a longer half-life, higher affinity for EGFR, and it has less antigenic effect since it is completely human antibody.11