April 15, 2024

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Nature Cancer: Will Collagen prevent cancer cell metastasis?

Nature Cancer: Will Collagen prevent cancer cell metastasis?


Nature Cancer: Will Collagen prevent cancer cell metastasis? Another mechanism of cancer metastasis revealed. 

Collagen is the code of youth and the key to not getting old. Many people hope to make their skin breakable and rejuvenate by supplementing collagen.


In fact, in addition to the anti-aging effect of collagen, a new study recently published in “Nature Cancer” believes that collagen may also prevent cancer recurrence and metastasis [1] .


Nature Cancer: Will Collagen prevent cancer cell metastasis?


Is Collagen Really So Magical? Can cancer patients eat more collagen supplements and pig trotters to prevent cancer recurrence and metastasis?


Cancer cells lie dormant for years because they sleep


According to statistics, up to 90% of the deaths of cancer patients are related to cancer metastasis [2] , and various complications caused by metastasis also make cancer patients miserable.


Why does cancer recur and metastasize?


In fact, cancer metastasis is not always a late event that occurs long after local progression of the primary tumor. Some recent evidences suggest that [3], some early stage cancers have also found the signal of cancer cell metastasis. However, after cancer cells metastasize, a magical phenomenon of “dormancy” occurs [4] , just like some animals in nature hibernate.


Unlike animals hibernating, cancer cells stay dormant for years after metastasizing elsewhere, which explains why some recurrences and metastases occur years or even decades later.


And cancer cells are not idle when they are dormant. They have been paying close attention to the signals in the body. As long as the environment in the body is conducive to their survival, they will wake up and proliferate wildly, forming headaches. Metastases.


Why do metastatic cancer cells appear dormant?


Some scientists speculate that it may be because cancer cells have moved to a new place and are “unfamiliar with the microenvironment” of the new place, so they have entered a state of “temporary mitotic arrest” [5, 6] . This dormant state allows cancer cells to sleep like “sleeping beasts” for many years without danger.


Cancer cells  have been waiting for recovery


Is there a way to keep cancer cells in a dormant state?


Recently, a new study has discovered a new mechanism by which cancer cells remain dormant! The study found [1] that the content of type III collagen in the tumor microenvironment around the cancer cells in the dormant stage is relatively high; when the content of type III collagen in the microenvironment decreases , cancer cells may be released from the dormant state and thus activated, leading to the occurrence of cancer cell recurrence and metastasis.


So the researchers thought, if the content of type III collagen in the tumor microenvironment is increased, can the cancer cells be kept dormant? In animal experiments, they found that after increasing type III collagen, cancer cells that had metastasized to various sites did indeed enter a dormant state.


The researchers believe [7] that type III collagen is secreted by the metastatic cancer cells after they enter the dormant state to maintain the dormant state; while in the dormant state, the type III collagen in the tumor microenvironment, It will further promote the expression of type III collagen, so that cancer cells can always be in a dormant state.


The phenomenon that cancer cells secrete this collagen and surround themselves is a bit like the “cocooning” behavior of a spring silkworm spinning into a cocoon and wrapping itself in it.


However, cancer cells that are “cocooning themselves” have always patiently waited for the opportunity to recover. Some studies have found [8] that cancer cells have a certain “adaptability” .

After they move to new places, they will interact with the surrounding tumor microenvironment, such as generating new immune responses. But over the years, cancer cells will slowly overcome these immune responses.

At this time, the balance of type III collagen maintaining a dormant state may be disrupted, and the cancer cells will be reactivated, thereby releasing the dormant state.


In addition, studies have found [9] that stress can “help” cancer cells to release their dormancy state by regulating the immune response, thereby accelerating the recurrence and metastasis of cancer. So if you want to keep cancer cells dormant, you must learn to release your stress.


Can eating food with Collagen recurrence and metastasis be prevented?


Since cancer cells can “cocoon themselves” by secreting type III collagen to maintain dormancy, if type III collagen is increased in the tumor microenvironment to induce cancer cells to remain in a dormant state, wouldn’t it be possible to avoid cancer recurrence and metastasis?


Regrettably, at present, the method of type III collagen for preventing cancer recurrence and metastasis has not yet entered the (human) clinical research stage.


Then some friends will ask, can the collagen eaten through the diet keep the cancer cells dormant all the time, thereby preventing recurrence and metastasis?


The answer is no !


Although collagen is widely present in the connective tissue of animals, it accounts for 25% to 30% of the total protein in mammals.

However, after the collagen ingested in the diet is digested and absorbed by the human body, most protein macromolecules will become small collagen peptides or amino acid small molecules, and the split amino acid small molecules will be used by various tissues or cells of the body, and Will not reassemble into the original collagen.


It is conceivable that collagen cannot be supplemented through diet; the supplements on the market that advertise that they can supplement collagen cannot actually be supplemented.


In addition, collagen is still a large family, and the common types are type I, type II, type III, type V and type XI. In the above study, only type III collagen was able to maintain the dormancy of cancer cells.


Some studies have found [10, 11] that type I collagen may reactivate cancer cells and relieve their dormant state. Therefore, the collagen ingested in the diet is not all type III collagen, but also contains collagen that can promote the growth of cancer cells.

Type I collagen for cancer metastasis, but you don’t have to panic too much. After all, type I collagen ingested in the diet will also become small molecules and will not re-synthesize type I collagen in the human body.


Sum up

In conclusion, type III collagen may become a new means of preventing cancer recurrence and metastasis!

We still have to wait, scientists are already working on ways to supplement type III collagen into the tumor microenvironment.

While eating supplements, pig trotters, etc., there is currently no evidence that collagen can be supplemented to prevent cancer recurrence and metastasis.


In fact, in order to prevent cancer cells from waking up from dormancy, in addition to increasing type III collagen in the tumor microenvironment, these methods can also be used to avoid cancer cell activation: Why does lung cancer recur? “Dormant” cancer cells are “awakened” like this…




[1] Di Martino, JS, Nobre, AR, Mondal, C. et al. A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy. Nat Cancer (2021).

[2] Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science. 2011;331(6024):1559-1564.

[3] Comen E, Norton L, Massagué J. Clinical implications of cancer self-seeding. Nat Rev Clin Oncol. 2011;8(6):369-377.

[4] Willis RA: The Spread of Tumours in the Human Body. Nature 133, 743 (1934).

[5]Phan TG, Croucher PI. The dormant cancer cell life cycle. Nat Rev Cancer. 2020;20(7):398-411.

[6] Klein CA. Framework models of tumor dormancy from patient-derived observations. Curr Opin Genet Dev. 2011;21(1):42-49.

[7] https://www.eurekalert.org/news-releases/937265

[8] Giancotti FG. Mechanisms governing metastatic dormancy and reactivation. Cell. 2013;155(4):750-764.

[9]Perego M, Tyurin VA, Tyurina YY, et al. Reactivation of dormant tumor cells by modified lipids derived from stress-activated neutrophils. Sci Transl Med. 2020;12(572):eabb5817.

[10]Barkan D, El Touny LH, Michalowski AM, et al. Metastatic growth from dormant cells induced by a col-I-enriched fibrotic environment. Cancer Res. 2010;70(14):5706-5716.

[11]Cox TR, Bird D, Baker AM, et al. LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. Cancer Res. 2013;73(6):1721-1732.

Nature Cancer: Will Collagen prevent cancer cell metastasis?

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