Lecture 25: Neoplasia Terms and Cell Cycle

how many stages are in a cell cycle?

5

1st stage of cell cycle

G1 phase

describe G1 phase (1st stage of cell cycle)

cell growth to prep for DNA synthesis

2nd stage of cell cycle

S phase

describe S phase (2nd stage of cell cycle)

DNA synthesis occurs

3rd stage of cell cycle

G2 phase

describe G2 phase (3rd stage of cell cycle)

second growth phase, preparing for mitosis

4th stage of cell cycle

M phase

describe M phase (4th stage of cell cycle)

mitotic phase (pro, meta, ana, telophases)

5th stage of cell cycle: 2 options:

re-enters cycle and divides again, or exits cycle and enters quiescence

quiescence

inactivity

2 major checkpoints inside the cell cycle

G1/S checkpoint, G2/M checkpoint

first cell cycle checkpoint

G1/S

describe G1/S checkpoint

controlled by kinases, checks for DNA damage

2nd cell cycle checkpoint

G2/M

describe G2/M checkpoint

controlled by kinases, checks for DNA damage/completeness of replication

3 divisions of cells

labile, stable, senescet

labile cells

always dividing (enterocytes/skin/marrow)

stable cells

quiet, but can divide when needed (hepato/renal cells)

senescent cells

permanentely non-dividing (neurons/myocardiocytes/myocytes)

what do telomeres do?

DNA caps that regulate how many divisions a cell can undergo

what mediates cell cycle arrest (senescence)?

p53 and retinoblastoma (Rb) - tumor suppressor genes

what is the most important tumor suppressor gene and is considered the guardian of the genome?

p53

what does p53 do?

causes cell cycle ARREST at BOTH G1/S and G2/M checkpoints

what does retinoblastoma (Rb) do?

allows cell to PROCEED through G1/S checkpoint

what triggers apoptosis when DNA damage has occurred?

p53

how does neoplasia occur?

when cells evade checkpoints/mutate, begin replicating uncontrolled

2 types of neoplasia

benign and malignant

latency

time before tumor is detectable

1 cm tumor present, how many cells are inside?

1 million

3 steps of tumor development

initiation, promotion, progression

initiation of tumor development

IRREVERSIBLE DNA damage, cells remain quiet

histology of initiation phase

increase in # of cells, but BM remains INTACT

promotion of tumor development

tumor growth advantages occur, can be REVERSIBLE

histology of promotion phase

enlarged/mass like, but not aggressive

progression of tumor development

IRREVERSIBLE stage, tumor now malignant

tumor cells

parenchyma

supporting structure of tumor

stroma

scirrhous response

formation of fibrous CT on histology, comes from tumor cells

factors produced by tumors to promote blood supply to the area

pro and anti-angiogenic factors

pro-angiogenic factor

vascular endothelial growth factor (VEGF)

anti-angiogenic factor

thrombospondin

describe vessels in neoplasms

tortuous, irregular, unstable, leaky

tumor invasion MECHANISM

tumor cells penetrate BM using proteases -> migrate through ECM -> invade vessel lumen

why is invasion NOT metastitis?

the cells are invading vessels in the CURRENT tumor

tumor metastasis MECHANISM

tumor cells circulate -> colonize in metastatic site

metastasis

spread of neoplasm from primary to secondary site, ENDING communication with the primary site

metastasis has occurred. what does this mean?

TUMOR IS MALIGNANT

mass

any proliferation of cells forming a gross lesion

cancer

implies malignant behavior

neoplasm is occurring. describe chronicity/severity

chronic and severe

capsule is present. is it malignant or benign?

benign

capsule is NOT present. is it malignant or benign?

malignant

anaplastic cells

poorly differentiated cells (cell organization/morphology lost)

immunohistochemistry (IHC)

brown pigment present on antigen of neoplastic tissues, uses to identify anaplastic cells

low magnification histology of neoplasm

looking for overall pattern

high magnification histology of neoplasm

looking at individual cells

what are these?

mitotic figures

anisocytosis

variation in cell size (looks at cytoplasm)

anisokaryosis

variation in nuclear size

pleomorphism

variation in cell shape

increased anisocytosis is present. what does this mean?

more cytoplasm is present, making cell larger

immunosurveillance

process of immune system attacking foreign cells (transplants/microbes/tumor cells)

what do tumor cells express that signal the immune system?

tumor specific/associated antigens

cells involved in INNATE immune response (1st line of defense)

NK cells and macrophages

describe adaptive immune response (2nd line of defense)

cell mediated (most-effective) and humoral

4 ways tumor cells inhibit/manipulate immune responses

alter MHC expression, mask antigens, tolerance, immunosupression

mechanism of tumors altering MHC expression

down regulates MHC2, so no CD4 response occurs. MHC 1 expressed to evade NK cells

how do tumors antigen mask?

don't express tumor antigen on cell surface

how do tumors become tolerant?

express self-antigens to avoid immune system

what do tumors use to cause immunosupression?

TGF-a and FasL

what does TGF-a do?

inhibits growth/activation of macrophages

what does FasL do?

triggers apoptosis of nearby T lymphs

2 types of tumors KNOWN to regress

papillomas and histiocytomas