The Minor Collagen Hypothesis
Collagen is a crucial protein that provides structural support and strength to tissues throughout the body. However, there is a group of highly specialized minor collagens that may play a critical role in cancer progression. Most research on the biology of collagens has focused on the abundant collagens, but the highly specialized minor collagens that are expressed only at certain developmental stages may be deregulated in cancer.
The Hypothesis
Minor collagens are widely expressed during embryogenesis, as they organize the extracellular matrix (ECM) to support tissue development. However, in adult tissues, minor collagens become restricted to a few specific organs and are expressed at very low levels.
Recent studies have suggested that minor collagens may become deregulated in cancer, where they are highly upregulated in tumor tissues. This upregulation is thought to occur as the ECM is reorganized during tumor development and progression. We have chosen to call this hypothesis “The Minor Collagen Hypothesis”. We hypothesize that minor collages, which are normally restricted to embryonic tissues, may become active again in adult tissues as cancer progresses. The Minor Collagen Hypothesis proposes that this reactivation may be a key component in in tumor growth and invasion by altering the composition of the ECM.
Applying The Minor Collagen Hypothesis in clinical research
Biomarkers are important for indicating the presence or severity of a disease, and in cancer, they are crucial for early detection, monitoring of cancer progression, and guiding treatment decisions.
In general, several collagen biomarkers are overexpressed in cancer. However, minor collagens may offer a more specific biomarker for certain types of cancer. For example, recent research has shown that certain subtypes of cancer-associated fibroblasts (CAFs) express specific minor collagens. These collagens can be detected in blood, making them potential targets for drug development aimed at CAFs.
This hypothesis offers researchers new possibilities and highlights the need for more specific biomarkers for cancer diagnosis and treatment that could lead to better patient outcomes. Identifying biomarkers that detect specific minor collagens could be a breakthrough in cancer research and might shed light on an overlooked aspect of cancer progression.
Minor collagens are typically expressed during embryogenesis or tissue development and are expressed at low levels afterward. In cancer, however, these specialized collagens are expressed again to form an environment conducive to cancer growth. The abundant major collagens are also expressed during tissue development and growth spurts in childhood and adolescence but tapers off in adulthood. The relative induction as a function of cancer is greater for the minor collagens compared to the major collagens. This could mean better biomarker performance.
