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Molecular Mechanisms of Bone Metastasis

written by: Nirvanagrewal•edited by: Paul Arnold•updated: 6/23/2009

The spread of cancer to the bones from other organs is called bone metastasis. When cancer of the breast, prostate and kidney metastasize to bones it leads to alteration in the structure of bones and their mineral components.

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    Mechanism of bone metastasis

    Metastasis of any cancer to the bones is explained on the basis of ‘seed and soil’ theory. According to this theory bone presents a suitable environment for the growth of cancerous cells. Cancer cells from the original tumor detach and travel through the bloodstream or lymph system to reach bones. The bone environment is made up of osteoblast, osteoclast, bone matrix and many other different types of cells that present a favorable ground for the invasion and growth of tumor cells.

    Even when cancer cells from other parts of the body invade bone they are still named after the site from where they originated. So breast cancer cells that metastasize to the bone are still called breast cancer cells as opposed to being dubbed bone cancer cells.

    When cancer cells from any other organ metastasize to the bone it affects the bone in two ways:

    • Cancerous cells may eat away the bone cells thus causing osteolytic lesions. These lesions make the bones weak and lead to easy fracture.

    • New cancerous cells are formed in the bone. These are called as osteoblastic lesions, and they make the affected bone painful.

    Both types of lesions are caused by the production of certain chemicals by the cancerous cells i.e.; chemokine receptor 4 (CXCR4), vascular endothelial growth factor (VEGF), and connective tissue growth factor (CTGF).

    Physical conditions such as hypoxia, acidic pH, and calcium ions also stimulate the growth of tumor cells in the bone. All these factors lead to phenotypic change of the original tumor cells and convert them into osteolytic and osteoblastic lesions.

    Transforming growth factor-β (TGF-β), insulin-like growth factor-I (IGF-I), and IGF-II, are also released by osteolytic lesions and these favor the proliferation of tumor cells. TGF-β triggers the metastasis of bone by inducing proosteolytic gene expression in cancer cells, with parathyroid hormone–related protein (PTHrP). Osteolytic breast and prostate cancer cell tend to express PTHrP.

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    Symptoms of bone metastasis

    Metastasis of cancer to bone results in a variety of symptoms:

    • The first and the most important symptom associated with bone metastasis is pain. Pain is not the diagnostic symptom, as there are many other conditions that cause pain in the bones.
    • Bones become brittle and are also prone to fracture. Usually long bones of the legs and arms break up easily.
    • Blood cells are formed by the bone marrow. If cancerous cells metastasize to bone marrow it may affect the production of red and white blood cells. If red blood cells are affected it causes anemia, and if white blood cells are affected it causes infection, fever and chills.
    • Blood calcium level shoots up because of the release of calcium from the affected bone. Increased blood calcium level may cause nausea, formation of stones, constipation and gastrointestinal symptoms.