Invasi Tumor Ganas

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    INVASI

    TUMOR GANAS

    Dr. Humairah Medina Liza Lubis, M.Ked.(PA), Sp.PA

    DEPARTEMEN PATOLOGI ANATOMI

    FK-UNIBA BATAM

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    Cancer: General Etiology andPathogenesis

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    Cellular Basis of Cancer

    Cancer is a collection of diseases

    characterized by abnormal anduncontrolled growth

    Cancer arises from a loss of normalgrowth control

    In normal tissues, the rates of newcell growth and old cell death arekept in balance

    In cancer, this balance is disrupted

    This disruption can result from

    1) uncontrolled cell growth or

    2) loss of a cell's ability to undergoapoptosis

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    Cancer Cell Do Not Grow Faster Than

    Normal Cells

    Rather, Their Growth is Just

    Uncontrolled

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    Benign tumorsgenerally do not

    spread by

    invasion or

    metastasis

    Malignant

    tumors are

    capable of

    spreading by

    invasion and

    metastasis

    Malignant versus Benign Tumors

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    Overview

    What is metastasis?

    Molecular mechanisms of metastasis

    Signalling pathways involved in

    metastasis

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    I) What is cancer metastasis?

    Cancer defines as a population of cells that have

    lost their normal controls of growth and

    differentiation and are proliferating without check.

    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.

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    Invasion and Metastasis

    Abnormal cells proliferateand spread (metastasize) toother parts of the body

    Invasion - directmigration andpenetration intoneighboring tissues

    Metastasis - cancer cellspenetrate into lymphatic

    system and blood vessels

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    Preferential metastatic sites

    Primary tumour 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

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    Determining factors

    Appropriate growth factorsor

    extracellular matrix environment

    Compatible adhesion siteson the

    endothelial lumenal surface

    Selective chemotaxisat which the organ

    producing some soluble attraction factors

    to the tumor cells

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    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 or single cells orsmall 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 wallsfollowed by growth of the disseminated tumor cells

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    Stages of metastasis

    Invasion : primary tumour cells enter

    circulation

    Circulation to the secondary site of tumour

    growth

    Colonisation: formation of secondary

    tumour

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    Tumor invasion

    1. Translocation of cells across extracellular

    matrix barriers

    2. Lysis of matrix protein by specific

    proteinases

    3. Cell migration

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    Components of invasion

    a) Matrix degrading enzymes

    b) Cell adhesion

    c) Cell motility

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    a) Matrix degrading enzymes

    Required for a controlled degradation of

    components of the extracellular matrix

    (ECM)

    The proteases involved in this process are

    classified into serine-, cysteine-, aspartyl-,

    and metalloproteinase.

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    Cell adhesion and metastasis

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    b) Cell attachment

    1. Integrin: cell-matrix adhesion

    2. E-cadherin/catenin adhesion complex:

    cell-cell adhesion

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    Metastasis per continuatum:

    Lewat rongga tubuh (body cavity) Contoh: Ca ovarium --- ke peritoneum

    Ca colon --- ke cavum peritoneum

    Ca paru --- ke cavum pleura

    Metastasis secara limfogen:

    Terutama pada carcinoma

    Pola penyebaran metastasis kelenjar limfemengikuti rute normal dari lymphatic drainage.

    contoh: Ca mamma - metastasis KGB axilla

    Ca paru metastasis ke KGB hilus

    Ca nasofaring metastasis KGB colli

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    Metastases secara hematogen

    Terutama pada sarcoma Dapat juga terjadi pada carcinoma

    Renal cell ca --- vena renalis

    Penetrasi ke vena > arteri, karena arteri memilikidinding > tebal lebih tahan

    Invasi pada vena --- sel tumor mengikuti aliran vena --- metastasis sering terjadi pada paru & hepar

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    Hepar yang mengandung metastasis kanker

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    TERIMA KASIH