Osteosarcoma is a primary malignant bone tumor characterized by the direct formation of immature bone or osteoid tissue by tumor cells. It represents the most common type of malignant bone cancer, predominantly affecting children and young adults. The etiology of osteosarcoma involves a combination of genetic and environmental factors, with a notable incidence in areas of rapid bone growth during adolescence. The clinical presentation of osteosarcoma often includes pain and swelling at the tumor site, with the long bones of the limbs being the most frequently affected areas, particularly around the knee. The management of osteosarcoma has evolved significantly, with treatment protocols now incorporating a multimodal approach that includes neoadjuvant chemotherapy, surgical resection with limb-salvage procedures when possible, and adjuvant chemotherapy. Despite these advancements, the prognosis for osteosarcoma patients remains variable, heavily influenced by factors such as tumor size, location, the presence of metastatic disease at diagnosis, and the response to chemotherapy. Ongoing research and clinical trials continue to explore new therapeutic strategies, including targeted therapies and immunotherapies, aiming to improve outcomes for patients with this challenging disease.
Figure 1 Mechanisms of osteosarcoma. (Beird, 2022)
CD44 is a cell surface glycoprotein involved in cell-cell interactions, cell adhesion, and migration. Playing a pivotal role in the biology of various cell types, CD44 participates in a wide array of cellular processes, including the regulation of growth, survival, differentiation, and motility. In the context of osteosarcoma, a highly aggressive bone tumor predominantly affecting adolescents and young adults, CD44 has been identified as a critical player in tumor progression and metastasis. Its expression in osteosarcoma cells is associated with enhanced tumor invasiveness and a propensity for metastasis, particularly to the lungs, which is a common site for osteosarcoma spread. CD44 mediates these effects through its ability to bind to its ligand, hyaluronan, facilitating not only the interaction with the extracellular matrix but also the activation of downstream signaling pathways that promote cell proliferation, migration, and invasion. Moreover, CD44 has been implicated in the regulation of cancer stem cells within osteosarcoma, contributing to therapy resistance and disease recurrence. Thus, CD44 not only serves as a marker for aggressive disease but also represents a potential therapeutic target for the development of novel treatments for patients with osteosarcoma.
ABCG2, also known as ATP-binding cassette sub-family G member 2, is a crucial membrane transporter protein implicated in the physiological process of transporting various molecules across extracellular and intracellular membranes. It belongs to the ATP-binding cassette (ABC) transporter family, playing a pivotal role in the efflux of xenobiotics and endogenous substrates, including anticancer drugs, from cells, thereby contributing to multidrug resistance, a significant challenge in cancer treatment. In the context of osteosarcoma, the most common malignant bone tumor, ABCG2 is of particular interest due to its involvement in cancer cell resistance to chemotherapy. Elevated levels of ABCG2 in osteosarcoma cells have been associated with a poor response to chemotherapeutic agents, as it actively pumps out drugs from the cancer cells, reducing their cytotoxic effects. Furthermore, ABCG2 is involved in the regulation of stem cell-like properties in osteosarcoma cells, contributing to tumor initiation, progression, and recurrence.
Nestin (NES) is a type II intermediate filament protein primarily known for its role in the structural organization of the cytoskeleton in fetal and adult stem cells, where it supports cell shape and movement. It is widely used as a marker for neural stem cells in neurogenesis, indicating its pivotal role in the development and differentiation of the central nervous system. In the context of osteosarcoma, a highly aggressive bone tumor commonly affecting adolescents and young adults, NES has been implicated in the disease's pathogenesis and progression. Research suggests that high NES expression in osteosarcoma cells correlates with enhanced tumor invasiveness and metastatic potential, making it a potential biomarker for prognosis and a target for therapeutic intervention. The exact mechanism by which NES contributes to osteosarcoma progression is still under investigation, but it is hypothesized that its expression might influence the migratory and invasive capabilities of cancer cells, possibly through modulation of the cellular cytoskeleton and interaction with other signaling pathways critical for cancer cell survival and proliferation.
Biomarker | Alternative Names | Gene ID | UniProt ID | Roles |
ABCG2 | ATP Binding Cassette Subfamily G Member 2 (Junior Blood Group); ATP-Binding Cassette, Sub-Family G (WHITE), Member 2 (Junior Blood Group); Placenta-Specific ATP-Binding Cassette Transporter; Mitoxantrone Resistance-Associated Protein; Breast Cancer Resistance Protein; Urate Exporter; CDw338; BCRP1; ABCP; BCRP; MXR; Multi Drug Resistance Efflux Transport ATP-Binding Cassette Sub-Family G (WHITE) Member 2; ATP-Binding Cassette, Sub-Family G (WHITE), Member 2; ATP-Binding Cassette Sub-Family G Member 2 | 9429 | Q9UNQ0 | The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue. Multiple transcript variants encoding different isoforms have been found for this gene. |
CCN1 | GIG1; CYR61; IGFBP10 | 3491 | O00622 | The secreted protein encoded by this gene is growth factor-inducible and promotes the adhesion of endothelial cells. The encoded protein interacts with several integrins and with heparan sulfate proteoglycan. This protein also plays a role in cell proliferation, differentiation, angiogenesis, apoptosis, and extracellular matrix formation. |
CD105 | Endoglin; CD105 Antigen; END; Osler-Rendu-Weber Syndrome 1; HHT1; ORW1 | 2022 | Q63961 | This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. |
CD44 | CD44 Molecule (Indian Blood Group); Hematopoietic Cell E- And L-Selectin Ligand; GP90 Lymphocyte Homing/Adhesion Receptor; Chondroitin Sulfate Proteoglycan 8; Extracellular Matrix Receptor III; Heparan Sulfate Proteoglycan; Phagocytic Glycoprotein 1; Hyaluronate Receptor; Hermes Antigen; CD44 Antigen; ECMR-III; HUTCH-I; Epican; CDW44; MDU2; MDU3 | 960 | P16070 | The protein encoded by this gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. |
MAPK7 | Mitogen-Activated Protein Kinase 7; Extracellular-Signal-Regulated Kinase 5; Big MAP Kinase 1; MAP Kinase 7; EC 2.7.11.24; BMK1 Kinase; MAPK 7; PRKM7 | 5598 | Q13164 | The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor type kinases, and G protein-coupled receptors. In response to extracelluar signals, this kinase translocates to cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported. [provided by RefSeq, Jul 2008] |
TSPAN31 | SAS | 6302 | Q12999 | The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is thought to be involved in growth-related cellular processes. This gene is associated with tumorigenesis and osteosarcoma. |
CAT | Product Name | Biomarker | Assay | Image |
TAB-128CL | Anti-Human CD44 Recombinant Antibody (RG7356) | CD44 | SDS-PAGE |
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ZG-0258F | Mouse Anti-ABCG2 Recombinant Antibody (ZG-0258F) | ABCG2 | WB |
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ZG-0115J | Mouse Anti-CD44 Recombinant Antibody (ZG-0115J) | CD44 | IHC |
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ZG-0590J | Rabbit Anti-CD44 Recombinant Antibody (clone 4B7) | CD44 | WB |
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ZG-0156U | Mouse Anti-NES Recombinant Antibody (clone 2C2F7) | NES | WB |
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ZG-0237U | Mouse Anti-CD44 Recombinant Antibody (clone 6G2D2) | CD44 | WB |
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VS3-FY8 | Recombinant Rabbit Anti-ABCG2 Antibody (clone R02-5C2) | ABCG2 | WB |
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VS3-FY293 | Recombinant Rabbit Anti-CD44 Antibody (clone R08-5J6) | CD44 | WB |
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For research use only. Not intended for any clinical use.
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