Bone cancer

In 2017, cancer was the second most common cause of death worldwide, while bone cancer was a major cause of morbidity and mortality. In the following, we provide an informative overview of bone cancer, its types, causes, and effects.

 

What is cancer?

Cancer is defined by uncontrolled cell divisions leading to increased cell growth. Normal cell growth is promoted by genes called proto-oncogenes. However, occurrence of mutations in the proto-oncogenes, the genes become oncogenes overstimulating the cell growth potentially resulting in cancer. In addition, there are other genes called tumor suppressor genes, which normally promote apoptosis (cell death) of mutated cells. If mutations occur in the tumor suppressor genes, resulting in silencing of the genes, the cell lacks the apoptosis property, and cancer may consequently occur.

 

 Primary versus secondary bone tumors

The uncontrolled cell divisions leading to uncontrolled cell growth can potentially result in tumor formation. Thereof, bone cancer is when bone cells divides uncontrollably, forming a bone tumor. If the bone tumor is confined and does not spread into surrounding tissues, the bone tumor is a benign tumor which is not cancerous. On the other hand, if the tumor invades surrounding tissue and metastasizes (spreads to another body part), the tumor is a cancerous tumor, called a malignant tumor. Moreover, the malignant tumor is categorized dependent on its place of origin and where the tumor is located. If the malignant tumor is located in the bone and arose from bone cells, it is categorized as a primary bone tumor. If the malignant tumor is located in the bone but arose elsewhere in the body and has spread to the bone, it is a secondary bone tumor. Secondary bone cancer often arises from tumors in breast- or prostate cancer, but also from the lungs, thyroid, and kidneys. Thus, the use of primary-or-secondary notation refers to the place of tumor origin.

 

Cancer’s lethality and spreading

When the early-stage malignant tumor grow at its primary site, the growth can induce local tissue destruction, obstructions, and others associated symptoms. However, these problems are normally not accountable for the cancer’s lethality, because these tumors can often be surgically removed. Instead, the most lethal attribute of cancer is later-staged malignant tumors’ tendency to metastatize, generating new tumors in other body parts. Thus, early cancer detection is uttermost important for a positive outcome in cancer treatment.

The distribution patterns of metastasis (the spread of cancer cells) are not random. On the contrary, each type of cancer favors a spreading to specific organs. For instance, prostate cancer nearly always spreads to the bones, causing bone cancer. Likewise, 75 % of female breast cancer patients in stage IV (metastasis phase) develop secondary bone cancer.

The underlying metastasis mechanisms of tumor cells, contributing to the spreading of cancer cells, are not entirely understood. However, some types of cancer can travel through the lymphatic channels and bloodstream, whereas others can spread directly through connective tissue.

In addition, why some cancer types prefer certain distant sites of metastasis is likewise not clear. However, it is believed that certain factors at specific metastasis sites provide a fruitful environment for specific tumor cells. For instance, some tumor cells may be attracted to specific growth factors supporting the growth of tumor cells. Thus, the tumor cells migrate towards sites enriched with specific growth factors. Bone marrow is a common metastasis site of many tumors, likely due to the rich growth factor environment and easy access from the bloodstream. 

 

Effects of bone cancer on bone regeneration

Primary and secondary bone cancer can affect the normal bone regeneration, causing increased susceptibility to fractures, pain, infections, and hypercalcemia (very high levels of calcium in the blood).

Normally, bone remodeling is a continued process during which the bones are renewed, consisting of two overall steps. In the first step, the bones are reabsorbed (broken-down) by the body’s osteoclasts, being specific bone cells. The second step involves the osteoblasts which build new bone, and in that way, the bones are renewed. However, bone cancers, particular secondary bone cancers, influence this renewal process resulting in aforementioned conditions which all reduce the patient’s functional status, quality of life, and chance of survival.

 

 

Primary bone cancers

Primary bone cancer is rare and accounts for much less than 1% of all new cancers diagnosed. There are four types of primary bone cancer, being osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma.

Osteosarcoma
Osteosarcoma is the most common bone malignant tumor. Osteosarcoma arises from osteoblasts of different sizes called pleomorphic, which produce too much osteoid tissue (immature bone tissue). Osteosarcoma often occurs in the metaphysis (the ends) of long bones, like in the arm near the shoulder and distal femur and proximal tibia (around the knee joint), where there are numerous cell division occurring. It often grows quickly and spreads to other body parts, including the lungs.  Osteosarcoma normally affects adolescent, but can occur in any bone, particularly in older adults. Mutations associated with osteosarcoma are likewise linked to other cancer types, such as mutations in the pRB protein and p53 protein.

Ewing’s sarcoma
Ewing’s sarcoma is a malignant bone tumor which is also mostly seen in adolescents. Ewing’s sarcoma is believed to arise from neuroectodermal cells. Furthermore, Ewing’s sarcoma is associated with chromosomal mutations, especially a translocation between the chromosome 22 and chromosome 11, resulting in the formation of an abnormal protein called the Ewing’s sarcoma protein. This protein influences the differentiation process of human mesenchymal stem cells and neuroectodermal cells, leading to the growth of Ewing’s sarcoma tumor cells. Ewing’s sarcoma can potentially affect various bones but often affects the femur and sacrum (base of the spine).

Chondrosarcoma
Chondrosarcoma is mostly observed in elderly people. Chondrosarcoma arises from chondrocytes which are cartilage-producing cells (cartilage is a type of connective tissue which covers the ends of bones and lines the joints). Chondrosarcoma typically forms in the pelvis, proximal fem (upper leg), and proximal humerus (shoulder). Normally, it grows slowly, but sometimes it can grow quickly and spread to other parts of the body.

Chordoma
Finally, chordoma is a very rare type, which forms in the bone tissue of the spine. Chordoma typically occurs in older adults, and normally forms in the sacrum (base of the spine) and at the base of the skull.

 

Possible causes of bone cancer

For now, there are no known causes of bone cancer. However, there are several identified risk factors that increase the probability of bone cancer development.

Firstly, previous cancer treatment with chemotherapy, stem cells transplantation, or radiation may cause cancer. Osteosarcoma occurs more frequently in people, who previously have received anti-cancer drugs or high-dose external radiation therapy. Furthermore, 5% of children undergoing myeloablative hematopoietic stem cell transplantation develop osteosarcoma.

Furthermore, certain inherited conditions may cause bone cancer. Yet, hereditary conditions account for a limited number of bone cancers. For instance, osteosarcoma is more frequently observed in children with hereditary retinoblastoma, especially if they have received radiation. Likewise, this is true for patients with Li-Fraumeni syndrome.

However, since there is still much to learn about the causes of bone cancer, further research in the field is crucial. Fortunately, the development of new technologies that have applications in cancer research, such as organoids, yield advances in disease modeling and drug development. Ultimately, these advances can help improve current and future bone cancer treatments.

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