When looking at Squamous cell carcinoma (SCC), we can see that it is the second most common form of skin cancer. Squamous cell carcinoma has jumped two hundred percent. SCC is charted at around 1.8 million cases in the U.S per year, right behind Basal cell carcinoma at 3.6 million cases per year. Rogers HW, Weinstock Jama Dermatol 2015, 151(10). Prone to forming on areas of skin with major sun exposure such as, arms, legs and head. It is also known to grow inside the body as well. Mainly the mucous membranes. That is the inner lining of organs and cavities in your body, including the lungs, mouth and rear. SCC includes two different types, Cutaneous and Metastatic. The difference between contracting the two is based off the amount of cancer you possess already. Cutaneous is a cancer that targets only the epidermis level of skin (top layer), as well as beyond the first layer. Metastatic travels to places in your body beyond the skin. SCC is known to target older individuals as well as those with a lighter skin tone, green or blue eyes and blond or red hair. Those with a history of smoking are a target as well. The cause of SCC is a mutation to the p53 gene. The easiest way for the gene to mutate is from sunrays and tanning beds. The entire job of the gene is to divide cells and create new ones. However, the mutation can cause an abundance of cells to be made which will then form into tumors.

Similarly, collagen like SCC also attacks the skin, collagen also works its way towards targeting muscles, bones, ligaments and tendons. Collagens job is to provide your body with structure and support. It does things like help the fibroblasts located in the dermis. This helps grow new cells. It replaces dead skin cells, makes a covering that protects organs, clots blood and gives elasticity and strength to the skin. There are five main types of collagens. However, we are looking at type three. Type three is found in your arteries, organs and muscles. Type three is found in hollow organs like the bowel, the uterus and blood vessels. Collagen three is a protein made up of identical peptide chains. These chains are called alpha chains, made up of glycine, proline and hydroxyproline.

Type three collagen has been noticed to have dormant cancer cells. Being that collagen is supposed to support and strengthen skin, regrow skin cells and do all these helpful things for your skin; it is ironic that cancer is still able to form. Cancer is mainly found in the head and neck region when referring to squamous cell cancer. “Normal cells produce collagen III, but we found that cancer cells use it to keep themselves dormant” – Dr. Bravo-Cordero. Regarding women and breast cancer, metastasis, the second form of SCC, is related to cancer deaths. Type III collagen is known to be a component of tumor stroma. It appears that, when compared to other forms of collagen, type three seems to be the most helpful in reducing cancer. Looking at collagen type one, it has a rich source of usable metabolic fuel for cancer.

Tumor cell dormancy versus cell proliferation. Dormant tumor cells tend to stay dormant for many years, in which case can be more harmful than helpful. Being that the cells are undergoing dormancy they can go undetected which could lead to a hyper aggressive form of metastases. On the other hand, cell proliferation is measured by how fast a cancer cell can duplicate its DNA and then divide into two more cells. The extracellular matrix or (ECM), a grid like system that is made from multidomain macromolecules, undergoes changes depending on the state of the tumor cell. ECM inside of a proliferative tumor cell take on a stiffer form.

The cell cycle inside of single cells starts with the G1 phase where the cell size increases. S phase follows afterwards where the cell goes through DNA-synthesis and DNA becomes duplicated. Finally, the G2 phase shows the cell checks for the finalization of DNA-replication and begins the preparation for mitosis. In a normal cell cycle process, a cell will go through multiple “checkpoints” to make sure it is fit to continue the cycle; in a metastatic tumor the cell will continue the process no matter what may be wrong with it. A cell will continue to divide whether it is cleared or not.

Cancer cells create an atypical collagen to produce a protective ECM. This helps with proliferation and their ability to repel T-cells. That being said, there is more collagen III present around single cells than collagen III for metastases. When looking at the images and bar graph it is apparent that single cells almost double the amount of collagen III that is had in metastases. Referring to the images located on page five.

“We observed that T-HEp3 cells co-injected with type III collagen grew significantly smaller tumors than any other collagens tested or the vehicle.” Nature Reviews Cancer (2016) [PubMed]. Type III collagen is also known to restrict metastasis from forming mammary tumors. This restriction could be another reason why T-HEp3 paired with collagen III keeps tumor size small. When collagen III is used, the number of cells present also takes a downsize.

Collagen III was able to minimize the number of cells entering the S/G2 phases. Looking at the number of cells present when using collagen I, you can see where the cell divides into two. However, using collagen III it is apparent that the cell does not divide within the same phases

Citations

Paper 1 Pg.1-2

Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatol 2015; 151(10):1081-1086

Merek Manual (2022) Squamous cell carcinoma, Cleveland clinic medical 4/15/22 M.J. Nielson, M.A. Karsdal 2016) Biochemistry of collagens 5/16/16

Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK. Extracellular matrix structure. Adv Drug Deliv Rev. 2016;97:4–27.

Paper 2 Pg.3-4

Martino S. Di, Julie, Akhter Tasmiah, Bravo-Cordero Javier, Jose Remodeling the ECM: Implications for Metastasis and Tumor Dormancy, National Library of Medicine 2021 Oct; 13(19): 4916

Yarwood Stephen, Hengst Ludger, Regulation of Cell Cycle Progression by Growth Factor- Induced Cell Signaling, National Library of Medicine 2021 Dec; 10(12): 3327