Could Our Own Proteins Be Used to Help Us Fight Cancer?

Summary:
Heat shock proteins or HSPs were seen in 1962 when Furruccio Ritossa noticed that when the temperature was raised in an incubator with fruit flies, the chromosomes of the flies puffed up at certain places. This reaction was due to activated genes initiating the work of encoded proteins or HSPs. These proteins later were noticed in other forms of life other than fruit flies. HSPs are produced in response to stressful conditions and work to keep cell activities working well. In general, HSPs work to prevent undesirable interactions and promote beneficial interactions between proteins.
Unlike proteins inside a cell, which have a limited number of “matches” with which it can interact, HSPs can associate with a plethora of proteins giving rise to the wide variety of jobs HSPs can perform. For example, HSPs often become involved in the shaping of proteins. Each amino acid is either hydrophobic or hydrophilic. The HSP60 protein has both hydrophobic and hydrophilic parts and works to change the shape of the amino acid chain. The HSP100 protein, in contrast, works with the HSP70 protein to disassemble damaged proteins or cause a folded protein to unfold. The HSP70 proteins work by binding to peptides, which are short stretches of amino acid sequences. When ATP is present the molecule’s peptide-binding cleft is open. When ATP is absent the cleft is closed by a structure on the HSP70 protein and the peptide is trapped. HSP70 can trap a variety of peptides and therefore can work in many cellular processes like assembling complex proteins and protecting proteins affected by high temperatures. HSPs can be used during emergency conditions to alleviate stress by rescuing essential proteins, dismantling and recycling damaged proteins, and keeping cell processes operating smoothly.
Along with responding to hazardous conditions, HSPs can be used to fortify immune responses. A protein named gp96, identified as a member of the HSP90 family, can initiate immune resistance to tumors. Since identical gp96 molecules are found in tumors and in normal tissues, it is not the structure of the amino acids that provides immunity to cancerous cells. In 1990 it was found that HSP70 from tumors could also elicit tumor immunity. However, immunization did not occur when the molecule interacted with ATP. The ATP was causing HSP70 to release any bound peptides. When either HSP70 or HSP90 comes from cancers or virus-infected cells they have peptides from cancer-specific or viral antigens. HSP molecules, therefore, have a vital role in the recognition of cancerous and virus-infected cells. Peptides composed of antigens made inside cells associate with various HSPs and are eventually put onto a specific class of proteins. Cells called T lymphocytes are able to recognize the peptide complexes and eliminate any that portray a diseased cell. The ability of HSPs from tumors or pathogen-infected cells to carry and display peptides is essential in the immunization of those tumors or intracellular pathogens.
HSPs help T lymphocytes to recognize harmful peptides by interacting with immune cells called antigen-presenting cells. These cells are in almost every tissue of the body and are used to present antigens from their surrounding to T lymphocytes. They do this by taking in an HSP-peptide complex through a receptor and then revealing it to the T lymphocytes. T Lymphocytes then destroy or fight off cancerous or infected cells. HSPs can also alert the immune system of danger by causing antigen-presenting cells to go through changes in reaction to the presence of HSPs.
By taking HSP-bound peptides from a patient with a tumor it is possible to purify the peptides and create a vaccine that could initiate an attack against tumor-associated cells. In many cases this process has been successful. It even seems as if the process could be used to treat infectious diseases like genital herpes and tuberculosis.
The specific heat shock protein HSP90 is proven to buffer harmful effects and cover up variations and genetic mutations. When this function of HSP90 is deterred by extreme conditions, the accumulated variations are revealed and natural selection can take place. A loss of the function of HSP90 may make cancer cells more sensitive to stress, which could allow them to be destroyed more easily by chemotherapy. HSP90 inhibiters are, therefore, being tested in cancer patients along with chemotherapy.
Cancer immunotherapy involving HSP-peptide complexes can be very effective. However, very high doses of HSPs can cause the suppression, rather than stimulation, of immune responses. One danger of treating various diseases with HSPs is that drugs changing HSP levels may harm systems dependent on the proteins. Scientists, however, have learned to avoid side effects while altering proteins. In conclusion, heat shock proteins or HSPs are known to play essential parts in cell functions. They help create, degrade, and protect proteins, protect cells from the effects of mutations, and even facilitate immunity by associating with cells involved in antigen presentation. Among the many known functions of HSPs, however, are many more that have yet to be discovered.


My Response:
I continually marvel at the complexity of the life God has given to all creatures. This article presented proteins, processes, and associations, which I never knew existed let alone played such a vital part in life functions. HSPs are involved in many processes to protect the body and defend against harmful factors. Cancer and other infectious diseases are devastating and harmful. However, the effects of these diseases would be more extreme if the body had no way to defend itself. I believe the immune system is one of the most phenomenal systems of the body. Our bodies are constantly faced with adversity and potentially hazardous conditions. Each cell of the immune system including HSPs has a specific and unique function. As the various cells work together, much like any cooperation of people work together, they are able to defend against unwanted, undesirable effects. The information in this article allowed me to appreciate the diligent and faithful functions of the body’s immune system. Our knowledge of the functions of various cells like HSPs is minimal although constantly increasing. Yet these functions, known and unknown, continue to take place to keep our bodies operating smoothly.

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