1) Cancer begins as abnormal cells that grow uncontrollably and can become invasive, spreading to other parts of the body. 2) There are several types of cancer including carcinomas, sarcomas, leukemias, lymphomas, and central nervous system cancers. 3) Metastasis is when cancer cells spread from the original tumor site through the bloodstream or lymphatic system and form new tumors in other parts of the body. The major steps in metastasis include invasion, circulation, arrest in distant organs, and growth of new tumors.

1. CANCER AND
METASTASIS
Speaker :Sandeep kumar

2. Tumor Or Neoplasm An abnormal cell that grow and
proliferate out of control
Benign Tumor As long as neoplastic cells do not become
invasive
A Tumor is considered a Cancer only if it is malignant i.e.
Invasiveness is a essential characteristic of cancer cell

3. •M o r e s e l f - s u f f i c i e n t t h e n n o r m a l c e l l s f o r g r o w t h a n d p r o l i f e r a t i o n
•I n s e n s i t i v e t o a n t i - p r o l i f e r a t i v e e x t r a c e l l u l a r s i g n a l s
•L e s s p r o n e t o u n d e r g o a p o p t o s i s
•D e f e c t i v e i n i n t r a c e l l u l a r c o n t r o l m e c h a n i s m s t h a t n o r m a l l y s t o p c e l l
d i v i s i o n p e r m a n e n t l y i n r e s p o n s e t o s t r e s s o r D N A d a m a g e
•I n d u c e a n g i o g e n e s i s
•M e t a s t a s i z e
•G e n e t i c a l l y u n s t a b l e
•E i t h e r p r o d u c e t e l o m e r a s e o r a c q u i r e o t h e r w a y s o f s t a b i l i z i n g t h e i r
t e l o m e r e s .
General Behaviors of Cancer Cell

4. Types of Cancer
Carcinoma - cancer that begins in the skin or in tissues that
line or cover internal organs e.g. adenocarcinoma, basal cell
carcinoma and transitional cell carcinoma.
Sarcoma - cancer that begins in bone, cartilage, fat, muscle,
blood vessels, or other connective or supportive tissue.
Leukemia - cancer that starts in blood-forming tissue such as
the bone marrow
Lymphoma and myeloma - cancers that begin in the cells of
the immune system.
Central nervous system cancers - cancers that begin in the
tissues of the brain and spinal cord.

5. Carcinogens
Any agent that provoke the development of cancer is called
carcinogenic
Carcinogenesis is linked to the Mutagenesis(i.e. cause
mutations)
Carcinogens are classified into 2 classes
1) Chemical carcinogen: Typically cause simple local
changes in nucleotide sequence and
2) Radiations such as x- Rays: Typically cause
chromosomal breakage and Translocation &
UV Rays: Cause specific DNA base alteration i.e. Point
mutation

6. CANCER AND THE CELL CYCLE
In cancer cells CDK4 and CyclinD is either
Mutated or over-expressed

7. A GENETIC BASIS FOR CANCER
Oncogene : genes whose products play important roles in
the regulation of biochemical activities within cells,
including those activities related to cell division
First discovered in the genomes of RNA viruses-called υ-onc
Later, the cellular counterparts of these viral oncogenes were
discovered in many different organisms, ranging from
Drosophila to humans called c-onc/normal celluar
oncogene/proto-oncogene

8. Rous sarcoma virus: First tumor-inducing virus
discovered in 1910 by Peyton Rous
Contains 4 different genes:
 Gag- which encodes the capsid protein of the virion;
 pol-which encodes the reverse transcriptase;
 Env- which encodes a protein of the viral envelope;
 v-src- which encodes a protein kinase that inserts into
the plasma membranes of infected cells, responsible
for tumor formation
v-src gene produces 100 times as much tyrosine kinase
as the c-src gene, oversupply of the kinase upsets the
delicate signaling mechanisms that control cell
division, causing unregulated growth

9. Structure of Rous Sarcoma Virus

10. MUTANT CELLULAR ONCOGENES
AND CANCER

11. CHROMOSOME REARRANGEMENTS
AND CANCER
Translocated chromosome9 22
Philadelphia chromosome causes
chronic myelogenous leukemia (CML)
The Tyrosine kinase function of the c-Abl
protein has been constitutively activated
by the bcr/c-abl gene fusion
White blood cells grow and divide
uncontrollably.

12. Tumor Suppressor Genes
Genes that are normally
involved in the restraint
of cell growth, also called
anti-oncogenes

13. Molecular Biology of Cancer Cell

14. Molecular Biology of Cancer Cell
The pathway by which Rb controls cell cycle entry

15. Molecular Biology of Cancer Cell
This system becomes abnormally activated early in tumor progression

16. What is cancer metastasis?
Metastasis is the process by which a
tumor cell leaves the primary tumor,
travels to a distant site via the
circulatory system, and establishes a
secondary tumor
Metastatic tumors

17. Preferential metastatic sites
Primary tumor Common distant site (s)
Breast’ adenocarcinoma Bone, brain, adrenal
Prostate adenocarcinoma Bone
Lung small cell carcinoma Bone, brain, liver
Skin cutaneous melanoma Brain, liver, Bowel
Thyroid adenocarcinoma Bone
Kidney clear cell carcinoma Bone, liver, thyroid
Testis carcinoma Liver
Bladder carcinoma Brain
Neuroblastoma Liver, adrenal

18. 5 major steps in metastasis
1. Invasion and infiltration of surrounding normal host
tissue with penetration of small lymphatic or vascular
channels;
2. Release of neoplastic cells, either single cells or small
clumps, into the circulation;
3. Survival in the circulation;
4. Arrest in the capillary beds of distant organs;
5. Penetration of the lymphatic or blood vessel walls
followed by growth of the disseminated tumor cells.

19. Steps in the Process of Metastasis

20. Molecular Changes in Metastatic Cancer Cell
 Over expression of Rho-family GTPase RhoC, mediate actin-
based cell mobility
 Epithelial to Mesenchymal transition: change in expression of
E- cadherin gene,required for cell cell adhesion

21. Tumor induce Angiogenesis
To grow , a tumor needs an adequate blood supply to
get sufficient O2 and nutrients so form new blood
vessels(Angiogenesis), and lymphatic vessels
(Lymphangiogenesis)
Hypoxia
HIF-1α(gene regulatory protein)
VEGF(pro-angiogenic factor)
Attract endothelial cells and stimulate growth of new blood vessels
Vessels not only supply nutrients & O2 but also provide escape route for
its cells to metastasize

22. Thank you