Type I and III Collagen and DTCs

  I received an email today talking about the benefits of type I and III collagen for skin and bone health and to help with joint pain and stiffness. That immediately sounded promising as I am at high risk of bone loss due to my postmenopausal state and aromatase inhibitor need to keep my estrogen levels as low as possible to prevent a recurrence of my cancer. I also love the idea of less joint pain and stiffness, which is also a side effect of my aromatase inhibitor, but also likely due to being in my 5th decade of life (surprised me too... apparently ages 0-9 is the 1st decade and you can go from there). So I read and then my brain starts cranking.

 I learn that the way collagen helps with bone health is due to its affect on bone marrow. Knowing that I am in a clinical trial that looks at my bone marrow, I do some research and find:

 From Google AI:

 Disseminated tumor cells (DTCs) interact with types I and III collagen in the extracellular matrix (ECM) to regulate survival, dormancy, and metastasis. Type III collagen often promotes dormancy in DTCs, while type I collagen induces stiffness that aids tumor progression, migration, and survival. 

Role of Collagen III (Dormancy and Stability)

• Dormancy Marker: Type III collagen is crucial for establishing and sustaining the dormancy of disseminated tumor cells, preventing them from forming active metastases.
• Signaling Mechanism: Binding of DDR1 on tumor cells to type III collagen triggers STAT1 signaling, maintaining a dormant state.
• ECM Niche: High type III collagen, often in a "wavy," non-aligned structure, is associated with indolent (inactive) tumor niches. 

Role of Collagen I (Progression and Migration)

• Stiffness & Migration: Type I collagen is the primary fibrillar collagen in the tumor stroma; its increased density and aligned, stiffened fibers promote cancer cell invasion and migration.
• Survival Signal: DTCs interact with type I collagen through integrins, activating signaling pathways like FAK (focal adhesion kinase) to promote survival and resist anoikis. 
• Anoikis is a specialized form of programmed cell death (apoptosis) triggered when anchorage-dependent cells, such as epithelial or endothelial cells, detach from the surrounding extracellular matrix (ECM) or neighbor cells. It acts as a critical mechanism to maintain tissue homeostasis and prevent misplaced cells from surviving and proliferating in inappropriate locations.

Implications for Metastasis

• Switching States: A reduction in type III collagen, accompanied by increased type I collagen and fiber alignment, can drive dormant DTCs to transition into aggressive, proliferative metastatic cells.

• Targeting Strategy: Targeting these ECM interactions, particularly maintaining high type III collagen or targeting type I-mediated signaling, is a potential strategy to keep disseminated tumor cells in a dormant state, say studies from PubMed Central (PMC) (.gov) and PubMed Central (PMC) (.gov).

 What may seem like a good suggestion for health could be life changing for someone with high risk of recurrence of cancer. While I do not have any DTCs present at this time (understanding the 40% chance of false negative for my first set of results), if I were to develop them, taking this supplement could lead to more aggressive, proliferative metastatic cells. Let's review that again...  aggressive, proliferative metastatic cells. No thank you! One could decide to take only Type III collagen which keeps DTCs in their dormant state, but the collagens available for use also include Type I. 

 All this to say that research, even of the most minor things, like collagen and turmeric, is essential to understand the role of common supplements in the ongoing treatments when living with cancer.

 Dissemination of CTCs and tumor dormancy. Breast cancer cells are shed in the proximal circulation where they are referred to as CTCs. Single CTCs or clusters of CTCs can disseminate and home to distant organs sites, where they are referred to as DTCs. DTCs are found predominantly in the bone marrow, but also lung, liver and the brain. While cellular dormancy typically refers to single DTCs or clusters of DTCs, dormancy of micrometastases also occurs, and these are characterized by a transient cell cycle arrest or an equilibrium of proliferation/apoptosis, respectively. DTCs can reawaken, eventually giving rise to macrometastatic lesions.