FAILURE TO FOLLOW-UP RESEARCH STUDIES SHOWING THE POTENTIAL OF
CELLULAR FIBRONECTIN AS A CANCER THERAPEUTIC AGENT
The discovery of Cellular Fibronectin in 1973 (1) has led to over 30,000 research papers mentioning and/or researching this remarkable evolutionary protein.(2) While this website describes many aspects of those research endeavors, this paper is presented to reassess instances wherein the research studies failed to grasp the significance of its therapeutic potential especially in cancers. The references included herein show that there have been experimental findings of fibronectin research in various in vitro and in vivo cancer studies that show great potential for clinical applications. However, there had not been a concerted effort to bring these successful research projects into clinical fruition. The intent herein is to rectify this omission.
When Dr. Richard O Hynes discovered what is now named “Cellular Fibronectin”,(cFN) he never imagined that a protein could be so large. At the present, there are several proteins even larger than cFN, however, these larger proteins contain enormous cFN sequences, thereby, linking them evolutionarily related to this fascinating molecule.
Some of its primitive modular sequences are found in bacteria, archea, protist, plants, and in many other primitive species, implicating that these ancient modules eventually evolved into the present day cFN. The present day highly evolved cFNs are absolutely essential for metazoan life.These facts also portend that this protein had at least a 2 billion years old evolutionary history.
All of the blood-clotting proteins of modern metazoan species, namely Plasma Fibronectin, Fibrin and Factor VIII, are progeny of cFN along with the important adhesive molecule Vitronectin. There are many evolutionary discoveries relating to cFN presented on this website. However, the quest herein will be devoted to the possible implementation of cFN derived cancer therapeutic agents.
The discoverer of cFN, Dr. Richard O. Hynes, and colleagues in a 1977 paper, showed that when a small amount of this large protein was applied to transformed cells, their morphologies became more normal and further, there was a restoration to their adhesive properties. (3)
Dr. Kenneth M. Yamada also demonstrated that cFN restored transformed cells back to a more normal morphology. He was first to identify the differences between Plasma fibronectins, and cFNs. His speculation in his 1979 paper that Plasma fibronectin was a later progeny of cFN proved to accurate many years later.(4)
THE SIMPLE LABORATORY FINDINGS THAT THE FIBRONECTIN PROTEIN MISSING FROM THE ORIGINAL TRANSFORMED CELLS BECOME RESTORED BACK TOWARD A NORMAL CELL TYPE IMMEDIATELY AFTER THE FIBRONECTIN IS ADDED IS ASTOUNDING! NO PRESENT DAY CANCER THERAPEUTIC AGENT DOES ANYTHING BUT CELL DESTRUCTION WHETHER CANCEROUS OR NORMAL.
Why wasn’t this remarkable discovery of possibly returning cancer cells back to normalcy not aggressively pursued? Several answers to that perplexing question may be that there was an naive dogma (still in existence) that cancers were mainly genetic and their destruction is the present paradigm. Any funding in cancer research that does not agree with the prevalent paradigm will not obtain government grants. There have been many papers showing in terms of simple math that when evaluating the epidemiology of varies cancers throughout the world irrefutable evidence show that cancers differ according to regions, environment, diets and the like. This was affirmed by a U.S Congress commissioned Epidemiological Study. (5)
The classic example, the low breast cancer rate in Japanese women living in Japan. However, when these same women move to the United States, their breast cancer rates become exactly like USA women. Therefore, it is not a genetic problem.
On this website there is a relatively recent example of cFN placed into the culture of a long term ovarian cancer cell line resulted in the cell line becoming more normal.
cFN when applied to a wound site inhibits cancer recurrence. (6) This simple clinical therapeutic application would save thousands of lives in all cancer surgeries. Cancer recurrence at cancer surgical wound sites remain as tremendous clinical problem.
The genetic sequences of cancer cells probably retain their ability to re-differentiate back to a more normal phenotype if given the cFN therapeutic INDUCTION POTENTIAL. cFN evolutionarily has been involved in the differentiation of normal cells; it may be able to re-differentiate cancer cell back to a normal state as seen evidentially in past studies.
- Alteration of Cell-Surface Proteins by viral Transformation and by Proteolysis. Richard O. Hynes Proc,nat. Acad. Sci USA Vol.70, No. 11, p3170-3174, November 1973
- Birthday of a Breakthrough: Fibronectin Research Proves Important, But Not As Originally Expected. Rabiya S. Tuma. Journal of the National Cancer Institute, Vol. 96 No.1, January 7,2004
- Restoration of normal morphology, adhesion and cytoskeleton in transformed ells by addition of a transformed-sensitive surface protein. Ali IU et al. Cell 1977:May11: 115-26
- Fibroblast Cellular and Plasma Fibronectins are Similar But Identical. Kenneth M. Yamada and Dorothy W. Kennedy. The Journal of Cell Biology. Volume 80, 1979, pages 492-498.
- The Causes of Cancer. Richard Doll and Richard Peto Oxford University Press 1981.
6.The role of fibronectin in tumor implantation at surgical sites. M Satya Murphy, et al.
Clin Exp Metastasis. 1993. 11, 159-173