A Placenta-Specific Gene Ectopically Activated in Many Human Cancers Is Essentially Involved in Malignant Cell Processes

Abstract

The identification and functional characterization of tumorspecific genes is a prerequisite for the development of targeted cancer therapies. Using an integrated data mining and experimental validation approach for the discovery of new targets for antibody therapy of cancer, we identified PLAC1. PLAC1 is a placenta-specific gene with no detectable expression in any other normal human tissue. However, it is frequently aberrantly activated and highly expressed in a variety of tumor types, in particular breast cancer. RNAimediated silencing of PLAC1 in MCF-7 and BT-549 breast cancer cells profoundly impairs motility, migration, and invasion and induces a G 1 -S cell cycle block with nearly complete abrogation of proliferation. Knockdown of PLAC1 is associated with decreased expression of cyclin D1 and reduced phosphorylation of AKT kinase. Moreover, PLAC1 is localized on the surface of cancer cells and is accessible for antibodies which antagonize biological functions of this molecule. These features, in summary, make PLAC1 an attractive candidate for targeted immunotherapeutic approaches. [Cancer Res 2007;67(19):9528-34]

Placenta-specific protein 1 (PLAC1) is a unique onco-fetal-placental protein and an underappreciated therapeutic target in cancer

“…Cancers, including uterine, ovarian and cervical cancers, induce expression of PLAC1 for precisely the same reason that trophoblasts express it-to aid in migration, invasiveness and proliferation. The sporadic but nonetheless important work done to date on understanding the role of PLAC1 in cancers, particularly the experiments done in breast cancer cells in which PLAC1 is ablated and the cellular proliferation, migration and invasiveness are impaired or ablated as a result [27,38], clearly nominate this gene as a therapeutic target. The potential for PLAC1 as an immunotherapy target is tantalizing.…”

“…However, several independent investigations demonstrating that a variety of human cancers induce PLAC1 expression appeared over the next two years. One group, searching for genes that are silent in most cells but robustly expressed in cancer cells, chose to focus on gametogenic and trophoblast cells [27]. The gene that immediately stood out was PLAC1.…”

Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo

“…32,33 Total cellular RNA was extracted from DCs with RNeasy Mini Kit (Qiagen, Hilden, Germany), reverse transcribed with oligo-dT 18 using Superscript II (Invitrogen, Carlsbad, CA, USA), and subjected to real-time quantitative analysis on ABI PRISM 7700 Sequence Detection System instrument and software (Applied Biosystems, Foster City, CA, USA) with QuantiTect SYBR Green PCR Kit (Qiagen). Reactions were performed in duplicates with specific primers amplifying the d2eGFP-encoding region (eGFP-sense, 5 0 -CACATGAAGCAGCACGACTTC-3 0 ; eGFPantisense, 5 0 -CACCTTGATGCCGTTCTTCTG-3 0 ; each 300 nM) with initial denaturation/activation for 15 min at 95 1C, and 40 cycles of 30 s at 94 1C, 30 s at 62 1C and 30 s at 72 1C.…”

Circulating Anti-PLAC1 Antibodies during Pregnancy and in Women with Reproductive Failure: A Preliminary Analysis

“…Plac1 expression has been demonstrated in all of the trophoblast lineages in the mouse including the labyrinth and in trophoblast giant cells that possess invasive characteristics and are important during the early stages placentation. Using a breast cancer cell line, Koslowski et al [12] demonstrated the importance of PLAC1 in modulating cell proliferation and invasion. Although there is no direct experimental evidence, the presence of anti-PLAC1 antibodies could potentially alter placentation during the initial phases of trophoblast invasion of maternal decidua, myometrium, and blood vessels.…”

“…Evidence from in vitro studies using the MCF-7 breast cancer cell line suggests that PLAC1 promotes cell proliferation and motility, processes essential to tumor survival [12]. Independent studies from Tchabo et al, Dong et al, and Silva et al reported the presence of anti-PLAC1 autoantibodies in some cancer patients [9][10][11].…”