Neoplasia (Molecular Basis) Flashcards
What are the three stages of direct invasion by neoplastic cells?
- Detachment from surrounding cells; 2. Degradation of basement membranes; 3. Adhesion to extracellular matrix then degradation of it, followed by acquisition of motility factors and migration
Define the term “tumor progression.”
The process by which cells that have undergone neoplastic transformation acquire more and more characteristics that are deleterious to the host
Approximately how many different genes (of the tens of thousands of genes that comprise the mammalian genome) can, when mutated, lead to development of neoplasia?
Only a few hundred
In which two stages of the cell cycle do cells increase their mass in preparation for division?
G1 and G2 (G for growth)
Explain briefly the mechanism for development of tumor heterogeneity.
Tumor growth starts with a single cell that has undergone neoplastic transformation, and the incipient tumor develops by clonal expansion of this one cell. Initially, all cells in the mass are identical but, due to the lack of regulation of chromosomal integrity, the tumor cells acquire genetic changes that give rise to tumor heterogeneity.
Name two cell cycle checkpoints.
G1-S and G2-M
In a developing neoplasm, new subclones arise from descendants of the original transformed cell. What general characteristics are selected for in these subclones?
Subclones are more adept at evading host defenses and are likely to be more aggressive
List three of the general classes of proto-oncogene products.
- Growth factors
- Growth factor receptors
- Intracellular signal transducers
- Nuclear regulatory proteins
- Cell cycle regulators
Where in the cell cycle do the tumor suppressor genes p53 and RB cause cell-cycle arrest in response to DNA damage?
At the G1-S checkpoint
What is the term for a normal gene (i.e., a sequence of DNA) that regulates the growth and differentiation of a cell?
A proto-oncogene
Explain the “soil and seed” hypothesis of metastasis.
This theory states that interactions between the cancer cell (the “seed”) and the host target organ (the “soil”) determine where metastatic tumors arise. The “soil” can potentially have more favorable or less favorable conditions for metastasis. Since extravasation requires adhesion to endothelial cells, tumor cell attachment may be directed to specific sites by receptor and ligand interactions.
What happens at the two cell cycle checkpoints G1-S and G2-M, and why?
The cell cycle arrests while DNA is checked for fidelity. If DNA damage or infidelity is detected the cell can attempt to repair it or direct itself to undergo apoptosis. This prevents mutations becoming embedded within the genome, which could potentially lead to neoplasia.
The immune system provides antitumor mechanisms. Name two cell types responsible for the more specific of these mechanisms (i.e., those requiring antigen-specific priming by dendritic cells).
- T lymphocytes (cell mediated immunity)
- B lymphocytes (humoral immunity)
Tumor suppressor genes (TSGs) encode proteins that have two major functions. What are these two functions?
- Arrest cell cycling to allow a cell “breathing time” to detect and repair DNA damage; 2. Direct a cell to undergo apoptosis if DNA damage is irreparable
The immune system provides antitumor mechanisms. Name two cell types responsible for the less specific of these mechanisms (i.e., those not requiring antigen-specific priming by dendritic cells).
- Natural killer cells
- Macrophages
All cells in a developing neoplasm are, early on, identical clones. True or false?
True. Tumor growth starts with a single cell that has undergone neoplastic transformation, and the incipient tumor develops by clonal expansion of this one cell.
What is the term for the process by which cells that have undergone neoplastic transformation acquire more and more characteristics that are deleterious to the host?
Tumor progression
Expression of proto-oncogenes causes cancer. True or false?
False. Proto-oncogenes are normal genes that regulate the growth and differentiation of cells. Their expression is normal and necessary, but is very tightly regulated. When proto-oncogenes are mutated, and their expression becomes dysregulated (uncontrolled), proto-oncogenes are termed ONCOGENES.
All cells in a developing neoplasm are initially identical. However, due to the lack of regulation of chromosomal integrity, the tumor cells acquire genetic changes that lead to development of different populations of subclones. What is the term for this?
Tumor heterogeneity (tumor progression is OK too)
By the time most tumors become clinically evident, they have probably been developing in the host for many years. True or false?
True. The smallest clinically detectable mass is about 1cm in diameter and contains about one billion cells. To form a tumor that size, a single transformed cell must undergo about 30 rounds of cell division. Thus, by the time most tumors become clinically evident, they have probably been developing in the host for many years.
What is the term for a cell that has gained the ability to replicate more than a certain, predetermined number of times?
Immortalized
With progressive growth, a tumor mass becomes enriched for subclone variants with certain “skills,” all of which are bad news for the host. Name 5 “skills” that can be selected for in neoplastic cells.
- Metastatic ability; 2. Invasive ability; 3. Requirement for fewer growth factors; 4. Failure to express antigens (thus evading the immune system); 5. Resistance to chemotherapy; 6. Resistance to radiation therapy; 7. Ability to survive with little oxygen; 8. Ability to resist cold or heat; 9 … etc.
What is the term for the development of new blood vessels, such as that induced by developing neoplasms?
Angiogenesis
How tightly regulated is the expression of the various proto-oncogenes?
Very tightly regulated. [Dysregulation of proto-oncogenes can lead to inappropriate expression of their product, which may lead to neoplasia.]
Explain why cells with defects in proofreading genes are at higher risk for development of neoplasia.
These cells have impaired production of the proteins that check copied DNA for fidelity. Errors in DNA replication (e.g., mismatched bases) are not detected and so accumulate In the genome at an increased rate. If these errors are within critical genes such as proto-oncogenes or tumor suppressor genes the cell may be predisposed to development of neoplasia.
