Placenta-Specific Proteins in Cancer Biology

Placenta-specific proteins, exemplified by Placenta-Specific Protein 1 (PLAC1), are normally confined to trophoblast cells yet are aberrantly re-expressed across a range of malignancies. This oncofetal pattern reflects shared characteristics between trophoblast invasion and tumour progression, including immune evasion, angiogenesis and extracellular matrix remodelling. Ectopic expression of these proteins may facilitate neoplastic cell proliferation, migration and metastatic potential through the activation of signalling circuits such as the PI3K/AKT and Notch pathways. Their restricted expression in normal adult tissues renders placenta-specific proteins attractive biomarkers for early detection and monitoring, and promising therapeutic targets. Recent efforts have focused on elucidating transcriptional control mechanisms, mapping protein–protein interactions that drive oncogenic signalling, and translating these insights into targeted interventions. The global burden of cancer underscores the potential for placenta-specific antigens to inform both fundamental understanding of tumour biology and the development of precision immunotherapies.

Research from Nature Portfolio

A pioneering study demonstrated the feasibility of an antibody–drug conjugate directed against PLAC1 in prostate cancer. In this work, a high-affinity anti-PLAC1 monoclonal antibody was linked to a potent cytotoxic payload. Upon binding to PLAC1-expressing tumour cells, rapid internalisation delivered the drug to intracellular compartments, achieving selective apoptosis with minimal off-target effects in preclinical models. This approach not only validated PLAC1 as a surface antigen amenable to targeted therapy but also generated compelling evidence for a new class of immunoconjugates capable of discriminating cancer cells on the basis of ectopic placental antigen expression.

Placenta-Specific Proteins in Cancer Biology publication trend

The graph below shows the total number of articles in placenta-specific proteins in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

PLAC1: A trophoblast-specific membrane protein aberrantly expressed in various cancers, implicated in tumour growth and invasion.

Antibody–drug conjugate (ADC): A targeted therapy in which a monoclonal antibody is chemically linked to a cytotoxic agent for selective tumour cell killing.

Trophoblast: Specialized placental cells responsible for implantation, nutrient exchange and modulation of maternal immunity during pregnancy.

Notch1 intracellular domain (NICD): The active fragment of the Notch1 receptor released by proteolytic cleavage, acting as a transcriptional regulator in cell fate decisions.

PTEN: A lipid phosphatase and tumour suppressor that regulates PI3K/AKT signalling, often downregulated in cancer.

References

1. Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway. Molecular Oncology (2018).
2. Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate-based prostate cancer immunotherapy. Scientific Reports (2017).
3. PLAC1 is essential for FGF7/FGFRIIIb-induced Akt-mediated cancer cell proliferation. Oncotarget (2020).