TITLE

Role of polypeptide growth factors in normal and abnormal growth

AUTHOR(S)
Patt, Leonard M.; Houck, John C.
PUB. DATE
April 1983
SOURCE
Kidney International;Apr1983, Vol. 23 Issue 4, p603
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
In the preceding sections we have shown evidence that growth-promoting factors are involved in three basic situations. In normal embryonic development and function of mature organisms, growth factors such as NGF and EGF are of prime importance in supporting the necessary embryonic cell proliferation and the development of specific cell types. Other factors operate on subsets of mature cells during specialized functions such as inflammation. Included in this set would be factors such as CSF/MGF and Interleukin-2. Another basic function of growth factors has been shown to be wound repair and organ regeneration. This includes the well characterized PDGF and FGF as well as the various renotropic factors and liver growth factors. As these factors must operate in mature organisms with many different cell types and similar cell types in many locations, more specificity is needed than in embryonic growth. This has resulted in the organ specific factors such as the renotropins and in the unique delivery system of the PDGF. The recent discovery and characterization of the transforming growth factors has provided a possible connection between embryonic and normal developmental growth and the rapid cellular proliferation characteristic of tumor cells. The TGF not only interacts with receptors for normal growth factors such as EGF but are also detectable in low levels in normal tissue and embryos. The exact relationships between these various factors will have to await the determinations of more amino acid sequences for comparisons. The other tumor-related product, tumor angiogenesis factor, is also found in normal tissue and inflammatory reaction sites. Any presentation of the biological function of the various growth factors must include their role in the growth control process. Obviously, growth factors are involved in the initiation at some point of division in sensitive cells. As shown here, this process can be regulated by limiting the cell types sensitive for certain factors or by limiting the distribution of the factor as with the PDGF. There is also evidence for the presence of inhibitors of cell growth with, in many instances, specificities analogous to the growth factors presented here. We will not present a detailed discussion of the various growth inhibitors and their possible interactions with growth stimulators. A major obstacle to the assignment of roles to growth inhibitors has been a lack of well defined inhibitors with which to study their biological interactions. To date, no inhibitor has been characterized to the extent that EGF or NGF has been. This, combined with the inherent difficulties in studying growth inhibition free of nonspecific toxic effects greatly hindered the development of theories concerning interactions of growth factors and inhibitors. Generally, there are reports of growth inhibitors for most of the stimulators mentioned here. For example, there is considerable evidence for epidermal cell inhibitors [124, 125], as well as smooth muscle [126], liver [127–129], granulocyte [130, 131], lymphocyte inhibitors [132], and many others [6]. It has been proposed that cell growth is controlled by cell-specific, endogenous reversible inhibitors of cell division usually termed chalones [6, 7]. These chalones function normally to restrain cells from proliferation, possibly by preventing the actions of growth factors. There is some experimental evidence to suggest that the action of inhibitors may be counteracted by specific growth factors [133, 1341.. The general function of growth factors and growth inhibitors (chalones) is to keep the cell number in balance such as to maintain tissue homeostasis. The final determination of the relative role each plays in this process is yet to be resolved. There are many functions of a mature organism which require rapid local proliferation of a small population of cells or the continued proliferation of one specific cell type. Both growth stimulators and inhibitors are involved in the initiation, maintenance, and final cessation of cellular proliferation.
ACCESSION #
17673015

 

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