Matrix Mettaloproteinase 3 : A Potential Biomarker For Human Metastatic Osteosarcoma

Cancer, medically called ‘tumorigenesis’ (Thaker, Lutgendorf, & Sood, 2007, p.430) occurs when cells in the body orient themselves for malignant growth. Such cells show ‘self-sufficiency in growth signals’, are ‘insensitive to anti-growth signals’ and have ‘limitless replicative potential’ (Thaker, Lutgendorf, & Sood, 2007, p.430). Once a particular set of cells become malignant, the malignancy can spread to other set of cells in different organs due to ‘crosstalk’ between the affected cells and their surrounding ‘tissues’ and ‘micro-environments’(Thaker, Lutgendorf, & Sood, 2007, p.430).

This cancer is a bone cancer that attack the bones, especially large bones. This cancer is named osteogenic sarcoma(Osteosarcoma) for medical term (“Osteosarcoma”, n.d.). Osteosarcoma mostly affects people under 25 years old, and it can affect old people but it is really rare(“Osteosarcoma: An Introduction.”, 2012). When this cancer attacks, it grows bones, and any type of bone (“Bone cancer”,2013). This cancer is an ancient disease that we started to recognize in 1805. Most of the symptoms are on the bones (“Bone cancer”,2013). It also is not contagious so its not passed from person to person like other diseases.

Osteosarcoma is an ancient disease that still has some mystery behind it. Osteosarcoma is a type of cancer that starts in the bones. It is also the most common type of bone cancer, and makes up 65% of all bone cancer. However, it is a very rare cancer and has fewer than 20,000 cases per year in The USA. The cells that form an osteosarcoma make bone matrix, similar to osteoblasts. However, the bone matrix of an osteosarcoma is not as strong as a bone matrix from an osteoblast, and therefore is not as strong as normal bones. The most common age group affected by osteosarcoma is children and young adults. However, osteosarcoma can occur at any age. Osteosarcoma is most commonly found in areas of the bone that grow quickly, which is why children are more likely to get this type of cancer. The most common place to find osteosarcoma is the end of long bones, especially in the knee, distal femur, and proximal tibia. The proximal humerus is typically the most common site. The treatments of

Osteosarcoma(OS) is a primary malignant tumor of bone which is characterized by the formation of osteoid tissue. Although it is the most common malignancy of long bones after multiple myeloma [2], it is a relatively rarer entity in the craniofacial region. About 6% of Oss arise in the jaws .The estimated incidence of the new cases of Jaw OS (JOS) per year is 0 .07 in 100,000. (1) The etiology of OS is unknown, but some risk factors such as a previous history of ionizing radiation, alkylating agent, retinoblastoma and benign bone lesions such as paget disease and fibro osseous dysplasia have been associated with the development of head and neck OS.(2-4) JOS occur with a peak in the third through fifth decades of life. The mean age is

My last goal is to show my findings in a good and understandable fashion through this paper to help my readers understand more about Osteosarcoma. Audience Since osteosarcoma is a lesser known type of cancer, I want to tell about what it is, some symptoms of it, and why metastasized cancer is bad. By making my peers my specific audience, I will be able to help them better understand what osteosarcoma is and how it forms.

during adolescent growth, which could be why 80% of all osteosarcoma childhood cases occur in the lower long bones and at the time of puberty (Mirabello & Savage 5). The chances of a cell dividing uncontrollably are increased at a time of rapid cell growth when there is many more cells dividing that could go suddenly go uncontrolled, and therefore the answer of how osteosarcoma is ignited could lie in puberty. On the contrary, the answer may be found in a small gene that prevents osteosarcoma patients from responding well to the chemotherapy treatment.

Cancer is listed as the second most common cause of death in western countries; particularly, in adults. Though it has a long antiquity, its prevalence and incidence today is pervasive and the war on cancer has not been promising. Malignant neoplasia is characterized by uncontrolled growth and the ability to metastasize or spread from the original site. Cancer results from mutations that promote cell proliferation and inhibit cell adhesion (metastasis). According to the National Cancer Institute (2016), “Cancer can also spread regionally,

To illustrate the danger of canine osteosarcoma, imagine a ten-year-old Saint Bernard that has symptoms of bone cancer. The dog has extreme bone pain and loss of appetite. The dog’s owner and veterinarian decide to give the Saint Bernard pain medication. A few months later, the dog cannot walk and dies. Unfortunately, osteosarcoma is the most common type of bone cancer in larger dogs and there is no cure. The most effective way to treat canine osteosarcoma is with amputation and chemotherapy because it manages bone pain, improves the survival time, and increases the survival rate.

Multiple myeloma is a haematological malignancy characterised by the suppression of osteoblastogenesis and the inability to form bone8. The inhibition of the Runt-related transcription factor 2 (Runx2) which is a key transcription factor responsible for osteoblast differentiation is largely implicated in multiple myeloma4. Runx2 stimulates the generation of the bone formation markers alkaline phosphatase (ALP), osteocalcin (OCN) and collagen during early osteoblast differentiation9,10. Transgenic mice without the Runx2 gene exhibit a lack of osteoblast formation causing the arrest of both endochondral and intramembranous ossification11. The upregulation of bone resorption and a decrease in bone mass is a common feature of multiple myeloma, presenting clinically as lytic bone lesions12.

Osteosarcoma can be diagnosed many ways. Pursuant to the American Cancer Society (2014), if a person presents signs and

In this paper, Osteosarcoma will be taken apart by details. The symptoms, treatment, signs, and other details will be discussed and explained. In a normal bone for most people there are two types of cells; osteoblasts and osteoclasts. Osteoblasts are what build up our bones by forming the bone matrix and therefore gives us the strength in our bones. Osteoclasts on the other hand break down the bone matrix so that we don’t get too much of it and that helps the bones to keep its proper shape. In Osteosarcoma the osteoblasts are what help make up the cancer in the bones. The bones do not have as strong of a bone matrix. This type of cancer is most commonly found in kids and young adults. There are three forms of treatment but not

Rare and currently incurable multiple myeloma accounts for roughly 1% of overall cancers and 13% of hematological cancers (Palumbo & Anderson, 2011). This form of cancer involves the infiltration of malignant plasma cells into the bone marrow. The median age of diagnosed individuals equals roughly 70 years of age (2011). Multiple myeloma progression results in the deactivation of bone synthesizing osteoblasts and the activation of bone disassembling osteoclasts that cause osteolytic lesions that present as bone pain, fractures, and hypercalcemia (2011). In healthy human bone marrow, plasma cells usually comprise <5.5mg/mL showed a median survival of 44 months (2015). With current treatment

The uncontrollable spread of cancer is the principal event which leads to the death in individuals with cancer and it is the greatest barrier of developing cures for cancer. Metastasis is the progressive spread of malignant cancer cells from the primary tumour to secondary organ in distant sites and this potential is dependent on the specific microenvironment which support them to complete each step of the metastatic process (Poste &amp; Fidler 1980). To understand the molecular basis of metastasis, investigators have now separated the complex and highly selective metastasis process into series of steps to try and solve the problems cause by

The ability of cancerous cells to migrate from their primary site and invade a secondary site is a hallmark of malignant progression. The invasive potential of a tumor hinges on the rigidity of its epithelial microenvironment in vivo, or the stiffness of the matrix on which the cells are grown in vitro. The serine/threonine protein kinase Cα (PKCα) promotes cell movement and contributes to tumor invasion, partially due to its activity on two newly discovered substrates, CEP4 and α6-tubulin. We set out to characterize the role of these PKCα substrates in the invasive phenotype of an aggressive metastatic mammary carcinoma cell line LM2-4175. We hypothesized that phosphorylation-resistant mutants of CEP4 and α6-tubulin would decrease the invasive phenotype. To test this, we transiently transfected LM2-4175 cells with either wild type or phosphorylation-resistant CEP4 or α6-tubulin and studied their migratory efficiency in transwells fitted with matrices of differing stiffness. In parallel, cells were treated with a PKC activator. As predicted, migration was potentiated by stiffer matrices under all conditions, with the exception of cells transfected with phosphorylation resistant CEP4 and α6-tubulin where the invasion in the softer matrix was greater. Furthering our understanding of the individual contributions of substrates of PKCα holds clinical promise, as it will permit the development of novel targeted therapeutics to curb cell migration and metastasis.

The likely site of PCa metastasis is the metabolically active hematopoietic bone marrow. Tombal and Lecouvet (2012) report that bone metastases, specifically into the hematopoietic red marrow, represents the main and primary site of metastasis for 80% of PCa’s. The abundant vasculature within bone marrow provides malignant cells with ample oxygen and nutrients that are needed for successful establishment of a metastic lesion. Additionally, the nearby pelvic lymph nodes provide PCa with an efficient route of metastasis into the pelvis, hips, and lumbar vertebrates. Tumour cells achieve absorption into bone morrow through a process that is directed by tumour cells, but effected by osteoclasts (Koutsilieris et al., 2006). Tumour cells