TRANSFORMASI SEL & KARSINOGENESISDwi Yanti

PENGERTIANTransformasi SelPeralihan suatu sel-sel normal menjadi sel-sel tumorSel normal >> berdiferensiasi >> dihambat pembelahannya >> banyak di fase G0Sel tumor >> tidak berdiferensiasi >> membelah tanpa hambatan

Karsinogenesis Proses terbentuknya kanker dari awal terpapar sampai terbentuknya sel kanker. Memiliki beberapa tahapan dan terjadi dalam kurun waktu yang lama ( 15-25 tahun)

SEL NORMAL

Increasein growth factorsIncreasein growth factorreceptorsIncrease in signal transductionIncrease in activation of transcription- Disturbed processes of mitosis and protein synthesisSEL MALIGNA

KARAKTERISTIK SEL KANKER

09/28/09

MULTISTEP KARSINOGENESIS

Inisiasi: Mutasi pada gen yang mengendalikan pengaturan siklus sel (irreversible) defek protoonkogen, namun kehilangan fungsi gen supresor tumor juga dapat membantu terjadinya inisiasi.Promosi: Perbanyakan sel-sel yang terganggu karena inisiasi tumor. Proses ini dapat berlangsung sangat lambat, hingga bertahun-tahun.Progresi: Proses yang menyebabkan suatu tumor menjadi ganas melalui perbanyakan, invasi, dan metastasis.MULTISTEP KARSINOGENESIS

Multistep Carcinogenesis

Proto-oncogenes (activated oncogenes) code for:growth factorsreceptorssignal-relay or transduction factors EX: ras - colon cancer myc - lymphoma bcr-abl - chronic myelogenous leukemia (Philladelphia chromosome)

Tumor suppressor genes - code for factors that down regulate the cell cycle, promote differentiation and supress oncogenes from causing cancer Rb-1 retinoblastoma gene p53

REGULATORY GENE

09/28/09

09/28/09RbAktif: hipofosforilasiInaktif: hiperfosfolirasiTransisi G1/S

Networks p53Ling Bai and Wei Ghuo Zhu, Journal of Cancer Molecules 2(4): 141-153, 2006.

NEOPLASIA proto-oncogene is activated or tumor suppressor gene is inactivated

normal growth oncogenesis

Activation of proto-oncogene: point mutationtranslocationgene amplification

Also - Failure of Immune Surveillance theory : immune system responds to neoantigens as to foreign antigens, but neoplastic cells escape recognition and destruction --> become clinical cancers

1. Invasi penyebaran lokal - fase in situ - fase invasi Terdapat kepekaan jaringan tubuh terhadap invasi 2. Metastasis penyebaran jauh perjalanan : - invasi matriks ekstrasekuler - Penyebaran vaskuler - pertumbuhan sel tumor di tempat baruPENYEBARAN TUMOR GANAS

Invasi1. Cellular Multiplication2. Mechanical Pressure3. Release of Lytic Enzym ( Protease)Serine (Urokinase-type-plasminogen activator (uPA))Cysteine (cathepsin B, D)Matrix Metaloproteinase (MMP)4. Penurunan Adesi Sel Integrin: cell-matrix adhesionE-cadherin/catenin adhesion complex: cell-cell adhesion 5. Cell motility/migrationSmall Rho GTPase familyMotility promoting factors

Steps of Invasion

destruct near tissuedestruct far tissueInvasion and infiltration of surrounding normal host tissue with penetration of small lymphatic or vascular channels;Release of neoplastic cells, either or single cells or small clumps, into the circulation;Survival in the circulation; Arrest in the capillary beds of distant organs;Penetration of the lymphatic or blood vessel walls followed by growth of the disseminated tumor cells steps in metastasis

Preferential metastatic sites

Primary tumourCommon distant site (s)Breast adenocarcinomaBone, brain, adrenalProstate adenocarcinomaBoneLung small cell carcinomaBone, brain, liverSkin cutaneous melanomaBrain, liver, BowelThyroid adenocarcinomaBoneKidney clear cell carcinomaBone, liver, thyroidTestis carcinomaLiverBladder carcinomaBrainNeuroblastomaLiver, adrenal

Reason for organ selectivityMechanistic theory: determined by the pattern of blood flow.

Seed and soil theory: the provision of a fertile environment in which compatible tumor cells could grow

TERIMA KASIH&SEMOGA BERMANFAAT

*Characteristics of metastatic tumor.*