Scientific Literacy 1: Background Essay

Dormant cancer cells could reawaken due to a change in a key protein. Collagen is a key protein that has helped researchers in finding out different methods of figuring out where cancer is more easily spreadable and more active. 

Squamous Cell Carcinoma is a type of skin cancer that is small, flat cells that start on the outer layer of the skin. When Squamous Cell Carcinoma turns cancerous, they start to form a round skin tumor that can be flat or raised. This Cancer can be formed from another type of skin growth called actinic keratosis. They can be cured if caught early on, however, if cancer goes beyond the skin layer, not many people can live up to 5 years even with an aggressive treatment plan. The cancer cells usually do not spread but are more likely to when on the lip, vulva, and also on male genitalia. Squamous cell carcinoma has a higher risk factor of developing in those who are fair-skinned and fair-haired. Those who have been exposed to industrial pollutants such as arsenic, tar, and industrial oil also have a higher risk of developing Squamous cell carcinoma. Having Genital warts before can also make you part of the higher risk factor for Squamous cell carcinoma. 

Collagen 3 is fibrillar collagen, which means that it is a sub-group within the collagen family. Collagen plays an important role in inflammation associated with lung injuries, vascular disorders, and nonviral liver diseases.  When type 3 collagen and type 1 collagen are together it establishes the interstitial matrix. Type 3 collagen consists of only one alpha chain, unlike its other types. This type of collagen is rich in soft tissues and shows up most in the early stages of wound healing. 

Collagen influences cancer cell activity with an extracellular matrix. They can influence tumor cells in discoidin and tyrosine kinase receptors and also in some signaling pathways. They also regulate tumor progression.  Collagen 3 has a role in the microenvironment of the tumor by keeping metastasis characteristics of tumor stroma at bay. Depending on where the cancer is located, collagen 3 can be of help or influence the progression. However, it has been found that type 3 collagen affects the speed at which the cancer spreads easily to other parts of the body. 

 

Dormant tumor cells are in a non-proliferative state and not actively growing. A proliferative state means cells are multiplying and spreading. Dormant tumor cells are categorized with a dense, organized matrix with elevated levels of collagen depositions and multicellular proteins. Such proteins are thrombospondin 1. Thrombospondin could prevent cell growth or spread. Extracellular matrix or ECM for short, has been revealed that the dormant cancer cells bring together collagen III. Collagen III is needed for tumor dormancy which proliferates in tumor cells (HHS Public Access, 2022 pg. 2). Proliferative tumors however are constantly growing and dividing and the ECM levels are much different than their dormant non-proliferative counterparts. ECM is broken down by enzymes that are planted by proliferative cells. This allows them to infiltrate different sites where they become meta. Metastasis traveling to another site is where the pathogenic agent goes from one primary site to a secondary site, or when talking about metastasis by a cancerous cell (Wikipedia, 2023) Metastases are often thought of when referring to a less dense, more disorganized extracellular matrix. Most deaths related to cancer are caused by metastases which could occur years after the original tumor removal (HHS Public Access, 2022 pg. 2).

Cellular dormancy is also known as reversible growth (G0/G1) (HHS Public Access, 2022 pg. 2). Metastatic tumors have more cells going through mitosis while single cells have more dormant cells in the G0/G1 phase. Some factors that could be leading to increased proliferation in metastatic tumors can be changes in the tumor microenvironment, genetic mutations, and even alterations in signaling pathways. The differences in these cell cycle stages could impact how effective cancer therapies and treatments are toward the dividing tumor cells. Type III Collagen can activate signaling mechanisms in tumor cell dormancy (HHS Public Access, 2022 pg. 3). Collagen III is the most abundant collagen in dormant tumor cells when compared to proliferative tumors (HHS Public Access, 2022 pg. 5). Stromal collagen III can restrict metastasis from forming coming out of mammary tumors (HHS Public Access, 2022, pg 6). Single cells are affiliated with denser extracellular matrices that have higher traces of type III collagen. The high level of collagen III could restrict the growth of individual tumor cells. Metastases are more associated with lower levels of type III collagen which speeds the growth of tumor cells. These differences in levels of collagen could be affected by a number of factors but do assist with the development of cancer. 

Collagen III that have been found when using proliferative T-HEp3 cell lines has been found to grow smaller tumors than the other collagens that were tested alongside this.  When a nude mouse was injected with T-HEp3 and collagen on opposite sides of one another, they were observed to have a slower growth rate in the company of collagen III. (HHS Public Access, 2022, 6). Some people have found that DDR1 as the collagen receptor is responsible for this process. When the depletion of DDR1 from dormant cells concluded with the cells waking up (Nature Cancer 2022).