Metastasis

Medical Presentation

1. METASTASIS Done By : NOEL CHRISTIAN

2. METASTASIS Metastases , migration and spread of cancerous cells from a tumor to distant sites in the body, causing secondary tumors. M etastasis identifies a neoplasm as malignant. Examples: osteogenic (bone) sarcomas (lungs). The larger the primary neoplasm, the more likely is metastatic spread.

3. SIGNS AND SYMPTOMS At first, nearby lymph nodes are struck early. The lungs ,  liver , brain, and bones are the most common metastasis locations from solid tumors . In  lymph nodes , a common symptom is lymphadenopathy Lungs : cough ,  and  dyspnea Liver : hepatomegaly (enlarged liver),  nausea and   jaundice Bones : bone pain ,  fracture of affected bones Brain : neurological symptoms - headaches,  seizures ,  and vertigo . Some patients , do not show any symptoms .  When the organ gets a metastatic disease it begins to shrink until its lymph nodes burst , or undergo lysis.

4. INVASION- METASTASIS CASCADE

5. MECHANISM OF METASTASIS Summary involving metastasis : 1) L ocal invasion, 2) I ntravasation into blood and lymph vessels 3) Transit through the vasculature 4) E xtravasation from the vessels 5) Formation of micro-metastases 6) Growth of micro-metastases into macroscopic tumors . M etastatic cascade can be subdivided into two phases : ( 1) Invasion of ECM ( 2) Vascular dissemination and homing of tumor cells

6. (1) INVASION OF ECM ECM: basement membranes and interstitial connective Tissue. A carcinoma first must breach the underlying basement membrane , then traverse the interstitial connective tissue, and ultimately gain access to the circulation by penetrating the vascular basement membrane. T o metastasize, a tumor cell must cross several different basement membranes. Invasion of the ECM is an active process that requires four steps :

7. (2) Vascular Dissemination and Homing of Tumor Cells In the bloodstream , some tumor cells form emboli by aggregating and adhering to circulating leukocytes (platelets) ; aggregated tumor cells are thus afforded some protection from the antitumor host effector cells. F ree tumor cells or tumor emboli involves adhesion to the vascular endothelium, followed by egress through the basement membrane into the organ parenchyma by mechanisms similar to those involved in invasion. Many tumors metastasize to the organ that presents the first capillary bed they encounter after entering the circulation. O rgan tropism may be related to the following mechanisms: 1) Expression of adhesion molecules by tumor cells. 2) Expression of chemokines(chemotaxis) and their receptors . 3) Once they reach a target, the tumor cells must be able to colonize the site.

8. TUMOR INDUCES ANGIOGENESIS To grow a tumor, needs adequate blood supply for oxygen and nutrients. Thus, the form new blood vessels (angiogenesis) and lymphatic vessels ( lymphangiogenesis ) Vessels not only supply oxygen and nutrients but also provide and escape route for its cells to metastasize.

9. Malignant neoplasms disseminate (spread) by one of three pathways: (1) Spread by seeding within body cavities, (2) Lymphatic spread , (carcinomas) or (3) H ematogenous spread (sarcoma)

10. (1) SPREAD BY SEEDING Within body cavities C ancers of the ovary Neoplasms of the central nervous system ( medulloblastoma or ependymom )

11. (2) LYMPHATIC S PREAD Carcinomas Lung carcinomas Carcinoma of the breast Skip-Metastasis T he cancer cells seem to traverse the lymphatic channels within the immediately proximate nodes to be trapped in subsequent lymph nodes, producing so-called skip metastases. The cells may traverse all of the lymph nodes ultimately to reach the vascular compartment by way of the thoracic duct.

12. (3) HEMATOGENOUS SPREAD S arcomas , but carcinomas use it as well . A rteries are penetrated less readily than are veins . T he liver and lungs are the most frequently involved secondary sites in hematogenous dissemination . Renal cell carcinoma (renal vein) Hepatocellular carcinomas (portal and hepatic)

13. ORGAN-SPECIFIC TARGET “Seed and Soil " theory, Stephen Paget, in 1889 - I t is difficult for cancer cells to survive outside their region of origin, so in order to metastasize they must find a location with similar characteristics. For example, Breast tumor cells, which gather calcium  from breast milk, metastasize to bone tissue, where they can gather calcium from bone.

14. IN RELATION WITH PRIMARY CANCER Approximately 30% of patients with newly diagnosed solid tumors present with clinically evident metastases . An additional 20% have occult ( hidden or unknown) metastases at the time of diagnosis .

15. COMMON SITES OF ORIGIN Lung Breast Skin: melanoma (other skin tumors rarely metastasize) Colon Kidney Prostate Pancreas Liver Cervix

16. MANAGEMENT Once a cancer has metastasized it may still be treated -- Radiosurgery -- Chemotherapy   -- Radiation therapy -- Biological therapy   -- Hormone therapy -- Surgery or -- Combination of these interventions ("multimodal therapy"). The choice of treatment depends on a large number of factors : -- Type of primary  cancer -- The size and -- Location of the metastases

17. REFERENCES   Zlotnik A., Burkhardt A. M., Homey B., Homeostatic chemokine receptors and organ-specific metastasis, Nature reviews, 2007 Jump up^ Yvette Drabsch , Peter ten Dijke , TGF- β Signaling in Breast Cancer Cell Invasion and Bone Metastasis, J Mammary Gland Biol Neoplasia (2011) 16:97–108 Jump up^  Yoshida BA, Sokoloff MM, Welch DR, Rinker-Schaeffer CW (Nov 2000).    Syn , Nicholas; Wang, Lingzhi ; Sethi , Gautam ; Thiery , Jean-Paul; Goh, Boon-Cher (2016-05-03). "Exosome-Mediated Metastasis: From Epithelial-Mesenchymal Transition to Escape from Immunosurveillance ". Trends in Pharmacological Sciences. 37 (7): 606–17   Lujambio , A; Esteller , M (Feb 1, 2009). "How epigenetics can explain human metastasis: a new role for microRNAs.". Cell cycle (Georgetown, Tex.). 8 (3): 377–82.