A report on Carcinogenesis and Cancer stem cell

Cancers and tumors are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.
Figure 1: Stem cell specific and conventional cancer therapies
The central role of DNA damage and epigenetic defects in DNA repair genes in carcinogenesis
Figure 2: A normal cellular hierarchy comprising stem cells at the apex, which generate common and more restricted progenitor cells and ultimately the mature cell types that constitute particular tissues.
Longitudinally opened freshly resected colon segment showing a cancer and four polyps. Plus a schematic diagram indicating a likely field defect (a region of tissue that precedes and predisposes to the development of cancer) in this colon segment. The diagram indicates sub-clones and sub-sub-clones that were precursors to the tumors.
Figure 3. In the cancer stem cell (CSC) model, only the CSCs have the ability to generate a tumor, based on their self-renewal properties and proliferative potential.
Tissue can be organized in a continuous spectrum from normal to cancer.
Figure 4: In the clonal evolution model, all undifferentiated cells have similar possibility to change into a tumorigenic cell.
Many tumor suppressor genes effect signal transduction pathways that regulate apoptosis, also known as "programmed cell death".
Figure 5: Both tumor models may play a role in the maintenance of a tumor. Initially, tumor growth is assured with a specific CSC (CSC1). With tumor progression, another CSC (CSC 2) may arise due to the clonal selection. The development of a new more aggressive CSC may result from the acquisition of an additional mutation or epigenetic modification.
Multiple mutations in cancer cells
Figure 6: Hierarchical organisation of a tumour according to the CSC model
Figure 7: The concept of migrating cancer stem cells (MSC). Stationary cancer stem cells are embedded in early carcinomas and these cells are detectable in the differentiated central area of a tumor. The important step toward malignancy is the induction of epithelial mesenchymal transition (EMT) in the stationary cancer stem cells (SCS), which become mobile or migrating cancer stem cells. Stem cells divide asymmetrically. One daughter cell will begin proliferation and differentiation. The remaining MCS migrates a short distance before undergoing a new asymmetric division, or disseminates through blood vessels or lymphatic vessels and produces a metastasis.

CSCs are therefore tumorigenic (tumor-forming), perhaps in contrast to other non-tumorigenic cancer cells.

- Cancer stem cell

Rather, a subset of the cells in a tumor, called cancer stem cells, replicate themselves as they generate differentiated cells.

- Carcinogenesis
Cancers and tumors are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.

5 related topics with Alpha

Overall
A coronal CT scan showing a malignant mesothelioma Legend: → tumor ←, ✱ central pleural effusion, 1 & 3 lungs, 2 spine, 4 ribs, 5 aorta, 6 spleen, 7 & 8 kidneys, 9 liver

Cancer

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Group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.

Group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.

A coronal CT scan showing a malignant mesothelioma Legend: → tumor ←, ✱ central pleural effusion, 1 & 3 lungs, 2 spine, 4 ribs, 5 aorta, 6 spleen, 7 & 8 kidneys, 9 liver
Symptoms of cancer metastasis depend on the location of the tumor.
The GHS Hazard pictogram for carcinogenic substances
Share of cancer deaths attributed to tobacco in 2016.
The incidence of lung cancer is highly correlated with smoking.
Cancers are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.
The central role of DNA damage and epigenetic defects in DNA repair genes in carcinogenesis
Chest X-ray showing lung cancer in the left lung
Three measures of global cancer mortality from 1990 to 2017
Engraving with two views of a Dutch woman who had a tumor removed from her neck in 1689
University of Florida Cancer Hospital
CancerTreeMammal
An invasive ductal carcinoma of the breast (pale area at the center) surrounded by spikes of whitish scar tissue and yellow fatty tissue
An invasive colorectal carcinoma (top center) in a colectomy specimen
A squamous-cell carcinoma (the whitish tumor) near the bronchi in a lung specimen
A large invasive ductal carcinoma in a mastectomy specimen

Cancer stem cells often use oxidative phosphorylation or glutamine as a primary energy source.

Several studies have indicated that the enzyme sirtuin 6 is selectively inactivated during oncogenesis in a variety of tumor types by inducing glycolysis.

Diagram showing the position of the pancreas, behind the stomach (which is transparent in this schematic).

Pancreatic cancer

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Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass.

Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass.

Diagram showing the position of the pancreas, behind the stomach (which is transparent in this schematic).
The pancreas has many functions, served by the endocrine cells in the islets of Langerhans and the exocrine acinar cells. Pancreatic cancer may arise from any of these and disrupt any of their functions.
Jaundice can be a symptom, due to biliary obstruction from a pancreatic tumor.
Cross-section of a human liver, at autopsy, showing many large pale tumor deposits, that are secondary tumors derived from pancreatic cancer
Micrograph of pancreatic ductal adenocarcinoma (the most common type of pancreatic cancer), H&E stain
Micrographs of normal pancreas, pancreatic intraepithelial neoplasia (precursors to pancreatic carcinoma) and pancreatic carcinoma. H&E stain
The head, body, and tail of the pancreas: The stomach is faded out in this image to show the entire pancreas, of which the body and tail lie behind the stomach, and the neck partially behind.
Axial CT image with IV contrast and added color: Cross lines towards top left surround a macrocystic adenocarcinoma of the pancreatic head.
Abdominal ultrasonography of pancreatic cancer (presumably adenocarcinoma), with a dilated pancreatic duct to the right.
Fine needle aspiration of well-differentiated pancreatic adenocarcinoma, showing a flat sheet with prominent honeycombing. The disorganization, nuclear overlapping, and lack of uniform nuclear spacing provides a clue that is this adenocarcinoma (as opposed to non-neoplastic duct epithelium).
Pancreatic cancer metastasized – stage M1
Parts of the body removed in Whipple's operation
How the pancreas and bowel are joined back together after a Whipple's operation
Deaths from pancreatic cancer per million persons in 2012
Stage T1 pancreatic cancer
Stage T2 pancreatic cancer
Stage T3 pancreatic cancer
Stage T4 pancreatic cancer
Pancreatic cancer in nearby lymph nodes – Stage N1

Furthermore, cancer stem cells are usually not evident microscopically, and if they are present they may continue to develop and spread.

Bile acids may have a role in the carcinogenesis of pancreatic cancer.

Tumour heterogeneity

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Tumour heterogeneity describes the observation that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential.

Tumour heterogeneity describes the observation that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential.

These are the cancer stem cell model and the clonal evolution model.

The cancer stem cell model asserts that within a population of tumour cells, there is only a small subset of cells that are tumourigenic (able to form tumours).

Transmission electron micrograph of an adult stem cell displaying typical ultrastructural characteristics.

Adult stem cell

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Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues.

Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues.

Transmission electron micrograph of an adult stem cell displaying typical ultrastructural characteristics.
Stem cell division and differentiation: A – stem cells; B – progenitor cell; C – differentiated cell; 1 – symmetric stem cell division; 2 – asymmetric stem cell division; 3 – progenitor division; 4 – terminal differentiation

The TGFβ family of cytokines regulate the stemness of both normal and cancer stem cells.

Mammary stem cells provide the source of cells for growth of the mammary gland during puberty and gestation and play an important role in carcinogenesis of the breast.

Tribolium castaneum telomerase catalytic subunit, TERT, bound to putative RNA template and telomeric DNA (PDB 3KYL)

Telomerase

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Ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres.

Ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres.

Tribolium castaneum telomerase catalytic subunit, TERT, bound to putative RNA template and telomeric DNA (PDB 3KYL)
A conceptual diagram showing the protein component of telomerase (TERT) in grey and the RNA component (TR) in yellow
An image illustrating how telomerase elongates telomere ends progressively.
Figure 4:A) Tumor cells expressing hTERT will actively degrade some of the protein and process for presenting. The major histocompatibility complex 1(MHC1), can then present the hTERT epitote. CD8- T cells that have antibodies against hTERT will then bind to the presented epitote. B) As a result of the antigenic binding, the T cells will release cytotoxins, which can be absorbed by the affected cell. C) These cytotoxins induce multiple proteases and result in apoptosis (or cell death).
Figure 5: A) Human telomerase RNA (hTR) is present in the cell and can be targeted. B) 2-5 anti-hTR oligonucleotides is a specialized antisense oligo that can bind to the telomerase RNA. C) Once bound, the 2-5 anti-hTR oligonucleotide recruits RNase L to the sequence. Once recruited, the RNase L creates a single cleavage in the RNA (D) and causes dissociation of the RNA sequence.

The exact changes that allow for the formation of the tumorigenic clones in the above-described experiment are not clear.

Cancer stem cells that use an alternative method of telomere maintenance are still killed when telomerase's RNA template is blocked or damaged.