Human growth factors and tumor growth
Human growth factors are naturally occurring proteins that serve as signaling molecules, controlling cell growth, proliferation, and differentiation. They play a crucial role in various biological processes, including wound healing and development. However, in the context of cancer, certain growth factors can contribute to tumor growth and progression. Tumors often produce specific growth factors known as transforming growth factors (TGFs), which promote angiogenesis—the formation of new blood vessels. This is essential for tumor survival and expansion, as a steady blood supply delivers necessary nutrients and oxygen.
Various families of growth factors, such as the vascular endothelial growth factor (VEGF) and the epidermal growth factor (EGF), are involved in these processes. The signaling pathways activated by growth factors can lead to alterations in gene expression, sometimes resulting in uncontrolled cell proliferation or apoptosis inhibition. Notably, several mutations can cause the overproduction of active receptors that perpetuate growth signals without their normal ligands. Interestingly, some growth factors, such as TGFβ, can also inhibit cell growth, highlighting their dual roles in tumor biology. Understanding these dynamics is crucial for developing targeted cancer therapies and improving treatment outcomes.
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Subject Terms
Human growth factors and tumor growth
ALSO KNOWN AS: Mitogens, cytokines
RELATED CANCERS: Multiple endocrine neoplasia type 2, leukemias, breast cancers, colon carcinoma
DEFINITION: Growth factors are naturally occurring proteins that act as signaling molecules between cells and control cell growth and cellular differentiation. Most growth factors stimulate the proliferation of different cell types, but some are involved in inhibiting cell growth or even causing target cells to undergo apoptosis.
Classification of growth factors and their receptors is as follows:
- Platelet-derived growth factor family (PDGF, CSF-1, M-CSF, SCF)
- Vascular endothelial growth factor family (VEGF)
- Epidermal growth factor family (EGF)
- Fibroblast growth factor family (FGF)
- Insulin family: Insulin-like growth factors (for example, IGF-I, IGF-II)
- Hepatocyte growth factor (HGF)
- Neurotrophin family (for example, NGF, TRK family)
- Ephrin family (EPH): a subfamily of receptor tyrosine kinases, RTK
- Agrin family
- GDNF family
- Angiopoietins
- Discoidin domain receptors
- Orphan receptors
Where found: Naturally in the body
At risk: No specific risk group
Etiology and symptoms of associated cancers: The binding of a growth factor to its cell-surface receptor triggers an intracellular signal transduction pathway, leading to changes in gene expression. The receptors of many growth factors have intrinsic protein tyrosine kinases in their cytosolic domains, which transmit the growth signal by phosphorylating tyrosine residues on themselves or on one or more target proteins, thus initiating a cascade of events. Several mutations lead to the overproduction of constitutively active receptors, which transmit growth signals without the normal ligands.
Tumors need nourishment from blood vessels to continue growing. Many tumors produce growth factors called transforming or tumor growth factors (TGFs) that stimulate the growth of blood vessels (angiogenesis). Basic FGF, TGFα, and VEGF have angiogenic properties and are secreted by many tumors. The growth of the tumor increases the probability of new harmful mutations. The availability of blood vessels also facilitates metastatic processes.
Some growth factors like TGFβ can inhibit the growth of many cell types, including most epithelial and immune system cells. Loss of TGFβ-mediated growth inhibition contributes to the development and progression of various tumors. The TGFβ signaling pathway is also connected to the expression of extracellular matrix proteins, such as collagen, a lack of which may contribute to metastasis.
History: Rita Levi-Montalcini and Stanley Cohen discovered and characterized NGF and EGF at the beginning of the 1950s by testing growth-promoting extracts of animal tissues. In the following decades, other growth factors were isolated and characterized.
Bibliography
"Human Epidermal Growth Factor Receptor 2." National Cancer Institute, www.cancer.gov/publications/dictionaries/cancer-terms/def/human-epidermal-growth-factor-receptor-2. Accessed 20 June 2024.
Lappano, Rosamaria, et al. "Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment." Cancers, vol. 14, no. 3, 2022, doi.org/10.3390/cancers14030539.
Li, Tao, et al. “Platelet‑derived Growth Factor‑BB Mediates Pancreatic Cancer Malignancy via Regulation of the Hippo/Yes‑associated Protein Signaling Pathway.” Oncology Reports, vol. 45, no. 1, 2021, pp. 83-94. doi:10.3892/or.2020.7859.
Sarasola, María de la Paz, et al. "Histamine in Cancer Immunology and Immunotherapy. Current Status and New Perspectives." Pharmacology Research & Perspectives, vol. 9, no. 5, 2021. doi.org/10.1002/prp2.778.