CD98 Specific Neutra™ Antibody Products

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CD98 oncoprotein, also known as SLC3A2 (solute carrier family 3 member 2), is a multifunctional transmembrane protein that plays crucial roles in various cellular processes, including amino acid transport, cell adhesion, and signaling. The overexpression of CD98 in cancer cells is associated with increased proliferation, survival, and metastasis. CD98 also contributes to chemoresistance by regulating amino acid availability and signaling pathways involved in cell survival and drug resistance. Overall, CD98 oncoprotein is a promising target for cancer therapy, and understanding its molecular mechanisms in tumorigenesis and metastasis could lead to the development of novel therapeutic strategies for cancer treatment.

Its Gene ID: 6520, UniProtKB ID: P08195, OMIM ID: 158070

The Structure of CD98

CD98 functions as a heterodimeric complex with a heavy chain (CD98hc) and a light chain (e.g., CD98lc), forming the L-type amino acid transporter 1 (LAT1) or 4F2hc/LAT1 complex. The heavy chain spans the cell membrane multiple times, creating transmembrane domains that anchor the protein within the lipid bilayer. The extracellular region of CD98hc contains multiple cysteine residues involved in disulfide bond formation, contributing to the stability and structure of the protein. The light chain associates with the heavy chain through non-covalent interactions, forming a functional complex. In particular, the light chain is responsible for amino acid transport activity, serving as a subunit of amino acid transporters such as L-type amino acid transporter 1 (LAT1). This complex facilitates the transport of essential amino acids across the cell membrane, crucial for protein synthesis and cellular metabolism.

The Function of CD98

Research found CD98 plays significant roles in both amino acid transport and integrin signaling.

Amino Acid Transport

CD98 plays a crucial role in amino acid transport by forming a heterodimeric complex with specific light chains, such as LAT1. This complex functions as an amino acid transporter, facilitating the uptake of essential amino acids into cells. Particularly, CD98 enhances the transport of large, neutral amino acids across the cell membrane, which are essential for protein synthesis, cellular metabolism, and cell growth. This function of CD98 is essential for cellular metabolism, protein synthesis, and various other biochemical processes.

Fig.1 CD98 functions as an amino acid exchanger. (Ip, et al., 2016) Fig.1 CD98 amino acid transport in cancer.¹

CD98 mediates cell survival, proliferation and migration by interacting with integrins 1 and 3 through CD98hc. Moreover, CD98 influences integrin-dependent signaling pathways, such as those involving focal adhesion kinase (FAK) and Src kinases. These pathways regulate various cellular processes, including cell proliferation, survival, and migration. By modulating integrin signaling, CD98 contributes to the dynamic regulation of cell behavior in response to extracellular cues. Dysregulation of CD98-integrin signaling can contribute to pathological conditions, including cancer metastasis and inflammatory disorders.

Fig.2 CD98-Integrin signaling pathway. (Ip, et al., 2016) Fig.2 CD98 integrin signaling in cancer.²

Therapeutic Strategy Targeting CD98

CD98, a protein associated with various cancers, particularly lymphoma, leukemia, and lung cancer, presents a promising target for therapeutic intervention.

One approach involves hindering the transportation of amino acids, crucial for tumor growth, by blocking CD98 light chains. Pre-clinical studies have demonstrated the efficacy of molecular inhibitors of LAT-1, a transporter associated with CD98, in slowing tumor growth across multiple cancer types, including colon and non-small cell lung cancer. Moreover, recent research has highlighted the tumor-suppressive effects of LAT-1 inhibition in esophageal cancer.

Another strategy involves using antibodies to block the effects of CD98hc. In cancers such as colon, prostate, and bladder cancer, mouse monoclonal antibodies targeting CD98 have shown inhibition of tumor growth. Additionally, the identification of an anti-CD98 antibody (IGN523) through in vivo screening exhibited significant growth inhibition in acute myeloid leukemia and squamous cell carcinoma models. Phase 1 trials of IGN523 in patients with relapsed or refractory acute myeloid leukemia have shown promising results.

To overcome the limitations of antibody therapies, peptide vaccines have been designed based on epitopes of antibodies with anti-tumor activity. However, inducing anti-tumor immunity has proven challenging. Another approach involves tagging CD98 for lysosomal degradation, leading to its downregulation and limiting cell proliferation.

MicroRNAs offer another potential avenue for therapeutic intervention, with microRNA-7 shown to downregulate CD98 expression. However, it's essential to consider the potential detrimental effects on epithelial homeostasis when targeting CD98 functions.

Creative Biolabs offers a range of recombinant anti-CD98 antibodies for research purposes. These antibodies target CD98 in human species and can be used for various applications such as ELISA, western blotting, immunofluorescence, immunoprecipitation, and functional studies. The antibodies are available for inquiry and are intended for research use only, not for direct clinical applications.

REFERENCE

Ip, Hugh, and Tariq Sethi. "CD98 signals controlling tumorigenesis." The international journal of biochemistry & cell biology 81 (2016): 148-150.

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