Concept of tumor growth
Tumor growth is a prototypical form of tissue growth disorder that occurs under the action of a carcinogen and manifests as pathological changes in the structural elements of the tissue. A tumor is characterized by atypia of growth, metabolism, structure, and function. A fundamental feature of a tumor cell is its escape from the homeostatic control of the host organism: the cell ceases to obey regulatory signals.
Prototypical forms of tissue growth disorders also include hypertrophy, hypotrophy, hyperplasia, hypoplasia, dysplasia, sclerosis, and metaplasia. Among these, tumors occupy a special place as a process with autonomous growth.
Benign and malignant tumors
- Benign tumors: slow division, highly differentiated cells, preservation of normal morphology, absence of metastasis, expansive growth.
- Malignant tumors: rapid division, low differentiation, loss of normal cell shape, ability to invade and metastasize.
Depending on the tissue of origin, malignant tumors are classified as follows: from epithelium — carcinoma, from glandular epithelium — adenocarcinoma, from connective tissue (bone, blood, muscle) — sarcoma.
Invasion is the infiltration of a tumor into underlying tissues. Metastasis is the formation of secondary tumor foci at a distance from the primary (parent) node.
Causes and conditions of tumor growth
The direct cause of a tumor is a carcinogen, i.e., a factor capable of causing malignant transformation of a cell. By nature, carcinogens are divided into chemical, biological, and physical.
Conditions promoting the realization of carcinogenic action:
- genetic predisposition (mutations in suppressor genes, oncogenes);
- decreased activity of proteins controlling the cell cycle;
- weakening of the body's anti-carcinogenic mechanisms (immune surveillance, DNA repair systems, antioncogenes).
Chemical carcinogenesis
Most chemical substances are procarcinogens: by themselves they do not cause a tumor, but are converted into active carcinogens as a result of metabolism, predominantly in the liver. A classic example is aflatoxin, which is converted into an epoxide.
- Organic carcinogens: aflatoxins, epoxides, aromatic and polycyclic hydrocarbons, heterocycles, 2-naphthylamine, alkylating agents, free radical compounds.
- Inorganic carcinogens: arsenic, asbestos, nickel and chromium compounds.
- Endogenous carcinogens: certain bile acids, estrogens, amino acid metabolites.
Stages of carcinogenesis
Carcinogenesis, regardless of the nature of the factor, includes two main stages.
- Initiation — the interaction of a carcinogen with cellular DNA, primarily with proto-oncogene — a DNA segment encoding proteins that regulate division and growth. As a result of damage, the proto-oncogene turns into an active oncogene. They are distinguished into:
- genomic initiation — point mutation in a proto-oncogene (nucleotide substitution);
- epigenetic initiation — dysregulation of expression without changing the DNA sequence.
- Promotion — expression of the oncogene, phenotypic transformation of the cell, active division, and formation of the tumor node.
Biological and physical carcinogens
Biological carcinogens are oncoviruses. RNA-containing viruses include Rous sarcoma viruses and a number of leukemias; DNA-containing viruses include adenoviruses, papovaviruses (including human papillomaviruses), and herpesviruses. Initiation consists of the integration of the viral genome (or its copy) into the host cell DNA with the formation of an oncogene; this is followed by promotion and transformation.
Physical carcinogens are ionizing radiation and ultraviolet light. They directly damage DNA, causing mutations in proto-oncogenes with the same outcome: oncogene formation, immortalization, expression, and tumor transformation.
Antiblastoma defense: antioncogenes
The body has an antitumor defense system — antioncogenes that encode tumor suppressor proteins.
- The p53 protein detects DNA damage and acts in two ways: it halts the cell cycle in the G1 phase, providing an opportunity for DNA repair; in cases of severe, irreversible damage, it triggers apoptosis.
- The p27 protein blocks the transition of the cell from the G1 phase to the S phase, preventing the replication of damaged DNA.
Decreased activity of these proteins is one of the key conditions for the realization of carcinogenic impact and tumor development.
Key points
- A tumor is a prototypical form of tissue growth disorder with atypia and escape from homeostatic control.
- Benign tumors are highly differentiated and do not metastasize; malignant tumors grow rapidly, invade, and metastasize.
- Carcinoma originates from epithelium, adenocarcinoma from glandular epithelium, and sarcoma from connective tissue.
- Carcinogens are divided into chemical (mostly procarcinogens), biological (oncoviruses), and physical (ionizing and UV radiation).
- Carcinogenesis includes two stages: initiation (conversion of a proto-oncogene into an oncogene) and promotion (oncogene expression and transformation).
- Initiation can be genomic (mutation) and epigenetic (dysregulation of expression).
- The tumor cell acquires immortality and an autonomous proliferative potential.
- The p53 and p27 antioncogenes ensure cell cycle arrest, DNA repair, and apoptosis of damaged cells.