Covering Tumor Cells In Collagen Could Keep Cancer Asleep
In samples from cancer patients, researchers found type III collagen predicted tumor recurrence and metastasis. In the mice, infusions of collagen around cancer cells blocked their progression, forcing them back into dormancy.
This intervention aimed at preventing the awakening of dormant cells has been suggested as a therapeutic strategy to prevent metastatic outgrowth, Prof Bravo-Cordero says.
As the biology of tumor dormancy gets uncovered and new specific drugs are developed, a combination of dormancy-inducing treatments with therapies that specifically target dormant cells will ultimately prevent local recurrence and metastasis and pave the way to cancer remission.
How cancer cells remain inert for long periods before awakening to wreak havoc throughout the body has baffled experts for decades. The study, published in the journal Nature Cancer, solves a major mystery and opens the door to therapies using collagen as a cancer treatment.
Collagen 1 Increases Kv101 And Orai1 Expressions And Potentiates Their Co
We have previously reported that Kv10.1 regulates cell migration in breast cancer cells by regulating basal calcium influx through Orai1 . Here we investigated the effect of collagen 1 on Kv10.1 and Orai1 expressions. The expression of Orai1 and Kv10.1 was increased by collagen 1 at both mRNA and protein levels in both cell lines .3). mRNA of Kv10.1 and Orai1 were increased by collagen 1 in MCF-7 , and in T47-D cells . Western blotting experiments showed also an increase in the expression of Kv10.1 and the glycosylated form of Orai1 in both cell lines . Similar results were observed by confocal fluorescence microscopy , p< 0.01 ). In order to show a possible functional interaction between Kv10.1 and Orai1, we analysed Kv10.1 and Orai1 staining and their colocalization at the plasma membrane of MCF-7 cells by fluorescence microscopy. As shown in Figure 4Ba, Kv10.1 was co-localized with Orai1 only in the presence of collagen 1. Indeed, in the presence of collagen 1 the co-localization between these two channels reached 50% . These data demonstrated that collagen 1 not only induced an increase in Kv10.1 and Orai1 expression but also potentiated their co-localization and interaction leading to the regulation of basal Ca2+ influx in BC cells.
Collagen 1 increases Kv10.1 and Orai1 expression in both MCF-7 and T-47D cellsCollagen 1 promotes the co-localization of Kv10.1 and Orai 1 at plasma membrane in BC cells
Collagen 1 Overexpressed Kv101 And Orai1 Through Erk1/2 But Not Akt Pathway
Several studies have reported the activation of ERK and Akt pathways in cell survival in the presence of collagen 1 . We therefore investigated whether these pathways were regulated by collagen 1 in our models. Cells seeded on collagen 1 coating showed an increase in ERK1/2 phosphorylation in the absence of FCS when compared to their counterparts seeded on plastic , p< 0.05 ). However, collagen 1, in the same conditions, failed to activate Akt . In order to investigate whether ERK1/2 was involved in the collagen-dependent overexpression of Kv10.1 and Orai1, cells were seeded on collagen 1 coating and treated with the ERK1/2 inhibitor PD98059 during 24 h and 48 h. Western blot analysis in Figure 8B-8C showed that PD98059 treatment abolished the collagen-dependent overexpression of Kv10.1 and Orai1 in both cell lines. In fact, Kv10.1 and Orai1 expression was reduced respectively by 62.46 ± 5.02% and 62.73 ± 15.9% after 24 h treatment, and by 64.13 ± 6.4% and 73.3 ± 11.6% after 48 h treatment by PD98059 in MCF-7 cells and by 60.17 ± 17% and 58.65 ± 3% after 24 h treatment, and by 70.07 ± 20.4% and 56.88 ± 16.88 % after 48 h treatment in T-47D cells . Moreover, treatment with PD98059 during 24 h and 48 h completely suppressed the collagen-dependent survival effect in both MCF-7 and T-47D cells .
Collagen 1 increases Kv10.1 and Orai1 expression through ERK1/2 pathway
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What Happens If You Take Collagen Everyday
Studies have shown that daily collagen supplements can help make your bones denser, slowing the aging process that makes them brittle and helping your body to produce new bone. Oral collagen supplements have been shown to improve skin hydration and elasticity for older people. They might also help to lessen wrinkles.
Does Collagen Suppress Tumor Growth
That was the only study I found that showed a particular type of collagen suppressed tumor growth. A 2018 study found that type 1 collagen promoted breast cancer cell growth and the ability to migrate to distant parts of the body. Another 2018 study also showed that collagen type 1A1 promoted breast cancer metastasis.
Cell Lines And Culture Conditions
MDA-MB-231 were maintained in DMEM/F12 with 10% FBS and 1% Pen/Strep. BT549 cells were maintained in RPMI-1640 with 10% FBS and 1% Pen/Strep. MCF-10A cells were kind gifts from Michael W. Kilgore, University of Kentucky, Lexington, KY. MCF10A cells were cultured as previously described . Hs-578 T cells were kept as previously described . S1 and T42 cells are kind gifts from Dr. Mina J Bissell, and they were cultured as previously described . All the cells were tested for mycoplasma contamination every two months.
The Relationship Among Exosomes Micrornas And Collagen In Cancer
Recent studies have highlighted the relationship among exosomes, microRNAs and collagen in cancer .
Exosomes are membrane-enclosed structures that facilitate communication between cancer cells and the ECM to influence cancer cell survival, growth, and metastasis and the immune system . Cancer-derived exosomes induce the formation of CAFs in the collagen matrix to promote EMT and increase the secretion of MMP-14 to regulate collagen . In addition, collagen enhances exosome secretion . Collagen and exosomes form a mutually beneficial feedback loop to promote cancer progression.
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What Are Some Types Of Collagen Supplements
In recent years, collagen has become a popular edible supplement. You can buy it in gelatin, capsule, liquid, fruit chew, or powder form.
Collagen supplements comes in three types:
- Gelatin. If you boil collagen for a long time, you end up with gelatin, the most basic form of edible collagen. Thats because the larger proteins found in collagen get broken down into smaller proteins. Collagen is what thickens bone broth.
- Hydrolyzed collagen. Hydrolyzed collagen is the most common type of collagen supplement sold. In this form, the collagen is broken down into basic amino acids, making it easier for your body to absorb. Hydrolyzed collagen is also known as collagen peptides, collagen hydrolysate, and hydrolyzed gelatin.
- Undenatured type II collagen . UC-II is not broken down, so its harder for your body to digest and absorb.
Hydrolyzed collagens dissolve in both hot and cold liquids. You can add them to hot tea or smoothies. Gelatin only dissolves in hot liquid, so its not suitable for cold drinks.
Dont Take Your Meds As Prescribed
You may shrug off pain medication because you heard its addictive or it makes you constipated, nauseous, or woozy. But skimping on your medicine isnt smart.
Pain can sometimes interfere with your sleep, appetite, and ability to get around, Whiteson says. And that can make it harder for your body to heal. Ultimately, the goal is to get off medication, but not before youre ready.
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The Collagen And Cancer Connection
One of todays hottest trends in the health and wellness industry is collagen. Many people, especially women are on board to add this promising supplement to their daily routine. Adding it to their coffees, smoothies and even baking with it has become the popular thing to do nowadays. Collagen, also known as the fountain of youth, for its anti-aging and therapeutic benefits has very quickly gained much attention lately especially among those in the health movement. Collagen is the major insoluble fibrous protein in the extracellular matrix and in connective tissue. In fact, it is the single most abundant protein in the animal kingdom. It provides structural support in tissues and it can affect the development and biochemical functions of cells.
The industry circulates many Collagen Benefits claims which include, skin health, gut health, joint pain relief, bone loss prevention, muscle growth, stimulates hair and nail growth, weight loss, etc. These claims create a buzz that many swear by while others believe it to be just another trend. There are at least 16 types of collagen, but 8090 percent of the collagen in the body consists of types I, II, and III. Consuming collagen may have a variety of health benefits but is it safe for cancer patients?
Are There Any Negative Effects Of Taking Collagen
Additionally, collagen supplements have the potential to cause digestive side effects, such as feelings of fullness and heartburn . Regardless, these supplements appear to be safe for most people. Collagen supplements may lead to side effects, such as a bad taste in the mouth, heartburn, and fullness.
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Effects Of Collagen Density On Cancer Cells
Increased stiffness compared to healthy tissue is a characteristic of most solid tumors that render them detectable by palpation. The high stiffness of tumor tissue has been shown to correlate with increased deposition of collagen as well as increased crosslinking of collagen fibers .
The high ECM stiffness is not only a passive bystander of cancer, but can also affect and drive many stages of tumor progression from malignant transformation and increased metabolic adaptability to enhanced intravasation, facilitating metastasis . In healthy tissue, matrix stiffness also controls many important cellular functions, such as development and homeostasis . In vitro, substrate stiffness has been shown to affect naÃ¯ve mesenchymal stem cells, which when cultured on soft matrices, mimicking brain tissue, commit to a neuron-like lineage while when cultured on rigid matrices, mimicking collagenous bone, commit to an osteogenic lineage .
Indirectly, a stiff matrix is also capable of supporting tumor progression by favoring growth of endothelial cells and thereby stimulating angiogenesis . Additionally, matrix stiffening promotes the activity of the transcriptional co-activators Yes-associated protein and transcriptional coactivator with PDZ-binding motif , which in turn are required for CAF-induced matrix stiffening, creating a positive feedback loop further driving the cancer-promoting effects described above .
Kv101 And Orai1 Staining
MCF-7 cells were gently and briefly washed with buffer containing 1 mM MgCl2, 100 mM KCl and 20 mM HEPES at 37°C. Then the cells were fixed and permeabilizated using 4% paraformaldehyde in PBS supplemented with 40 g/mL digitonin for 10 min. Before staining, cells were washed three times with PBS and treated for 45 min with 10% normal goat serum at room temperature for non-specific sites saturation. The anti-Kv10.1 and the anti-Orai 1 antibodies were added at 1:100 dilution for 1 hour. Then, after a second NGS treatment, a secondary AlexaFluor® 633 conjugate antibody was used at 1:100 dilution for Orai1 detection . For Kv10.1 detection, a biotinylated anti-goat secondary antibody was first used at 1:50 dilution . Then, the cells were treated with a streptavidin AlexaFluor® 488 conjugate antibody at 1:500 dilution .
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Fuelling Breast Cancer Recurrence
Collagen within a residual breast tumor. Image credit: Walens et al. 2019
Breast cancer is the second-leading cause of cancer-related deaths in women. Recurrence of breast-cancer five or more years after initial diagnosis and treatment causes more than half of these deaths. This suggests that some tumor cells survived treatment and persisted undetected. These residual tumor cells may not grow for years and are often surrounded by other cells, including immune system cells. What role these surrounding immune cells play in triggering future growth of these residual tumor cells is not clear.
Many breast cancer patients receive chemotherapy, which kills all quickly dividing cells. Targeted therapies, which block signals necessary for cancer cell growth, are also used often. More recently, scientists have developed treatments that use a patients own immune system to fight off cancer. Scientists are currently studying whether combining these immunotherapies with chemotherapy or targeted therapies increases the likelihood of eliminating cancer. Learning more about the role surrounding immune cells play in allowing residual tumor cells to persist and regrow is important to understanding how to treat cancer more successfully and prevent recurrence.
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What Are The Side Effects Of Taking Collagen
The side effect of collagen is that it can cause skin problems. It can also cause a condition called hyperpigmentation. Hyperpigeonemia is a skin condition that can be caused by too much collagen in the skin. , which is the most common type of hyperprolactinemia. This condition is caused when the bodys natural production of the hormone prolactin is too low. The body cant produce enough prolaxin to keep the blood vessels in your skin open. When this happens, the collagen can build up and cause the condition. If you have hyperplasia, you may also have a problem with your blood vessel walls. In addition, collagen may cause your hair to grow too fast. You may have to have your scalp trimmed to remove excess hair.
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Is Collagen Stronger Than Steel
Pound for pound, collagen is stronger than steel, yet it remains flexible and pliable. When collagen is strong and healthy, its an impenetrable force that cancer cells cant break through. This is important for survival, because ninety percent of cancer deaths are caused by it spreading, known as metastasizing, to other tissues and organs. Collagen is the gatekeeper that either allows or prevents this spread from happening.
Should You Avoid Collagen If You Have Breast Cancer
While there is some research indicating the potential for collagen to slow metastasis, there is not enough evidence to recommend taking supplements after a cancer diagnosis or during treatment. Patients should always consult with their physician before taking any supplement, as some can interfere with treatment.
Collagen Xvii Inhibits Breast Cancer Cell Proliferation And Growth Through Deactivation Of The Akt/mtor Signaling Pathway
Roles Formal analysis, Investigation, Visualization, Writing original draft
Affiliation Faculty of Pharmaceutical Sciences, Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand
Affiliation Faculty of Pharmaceutical Sciences, Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand
- Pornchai Rojsitthisak,
Roles Funding acquisition, Writing review & editing
Affiliations Natural Products for Ageing and Chronic Diseases Research Unit, Chulalongkorn University, Bangkok, Thailand, Faculty of Pharmaceutical Sciences, Department of Food and Pharmaceutical Chemistry, Chulalongkorn University, Bangkok, Thailand
- Chizu Tanikawa,
Roles Writing review & editing
Affiliation Laboratory of Genome Technology, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Koichi Matsuda,
Roles Conceptualization, Writing review & editing
Affiliations Laboratory of Genome Technology, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan, Department of Computational Biology and Medical Sciences, Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
Are Collagen Supplements Safe For Breast Cancer Survivors
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The Role of Collagen The ScienceCollagen is used to support and protect, so naturally tumors twist it to their advantage. Tumors are often full of fibroblasts, the major cell type responsible for producing collagen. These cells pump out huge amounts of collagen, swaddling little pockets of tumor cells, called tumor nests, in blankets of collagen that keep damaging agents away. These collagen-rich regions form a physical barrier around tumor cells that keep chemotherapeutics, immune cells, antibodies, and other therapies from reaching the cells to kill them. The particular shape and character of collagen in a tumor has even been linked to how easily the tumor grows and spreads.Tumour BiologyScience SignalingBreast Cancer ResearchThe Bottom Lineand your doctor agrees with that
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Integrin Signaling Is A Key Mediator Of Chemoresistance In Tnbcs
To elucidate the underlying mechanisms of chemoresistance in TNBCs, we modelled the clinical acquired resistance by using xenografts of the well-established TNBC cell line, MDA-MB-231,. Tumor-bearing mice were continuously treated with either vehicle or doxorubicin, and the fast-growing vehicle-treated mice were sacrificed, and tumors were denoted as vehicle. When tumors from the doxorubicin-treated group exhibited initial response to therapy and shrunk, tumors from some of the mice were collected and denoted as sensitive. The rest of the mice were kept under doxorubicin treatment until their tumors exhibited re-growth at rates comparable to vehicle-treated tumors, and those tumors were classified as resistant . The average growth curves and the Waterfall plot showing tumor volume fold change over time for vehicle-treated, doxorubicin-sensitive and -resistant tumors are depicted in Fig. , respectively.
Fig. 1: Integrin signaling is a key mediator of chemoresistance in TNBCs.
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Metastatic Breast Cancer Up
We performed gene expression analysis on publicly available microarray data of lymph node samples from breast cancer patients. Human lymph nodes that contained metastasized breast cancer cells demonstrated an up-regulation of major ECM proteins, such as collagen, fibronectin and several types of integrins as shown in .
Gene expression changes in genes driving the interaction between the ECM and ECM receptors in human lymph nodes containing metastatic breast cancer cells.
Microarray gene expression data were obtained from human lymph nodes affected by infiltrating ductal breast carcinoma cells as compared to unaffected lymph nodes. Total RNA was isolated and prepared for hybridization to human Affymetrix Gene Chip arrays . The heat map and corresponding statistical analysis was generated using the Gene-e matrix visualization and analysis platform . FDR < 0.05 was considered significant.
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