Embryonal Carcinomas (EC) are the stem cells of teratocarcinomas. Teratocarcinoma consists of teratoma and Embryonal Carcinoma. Teratomas are the tumors containing the differentiated somatic cells and Embryonal Carcinoma are the undifferentiated epithelial cells with resemble cells of the ICM (inner cellular mass) of blastocyst. Teratocarcinomas of the testis are of greater significance to cancer biologists due to their histological complexity, place of origin and germ cells always being the point of origin. All the testicular cancers are caused by germ cell tumors (GCT) and GCT are further divided into seminomas and non-seminomas. Seminomas consist of cells that resemble primordial germ cells while non-seminomas are a confusing batch which sometimes resemble seminomas itself.
Teratocarcinomas were not studied in detail till 1957 but when Stevens and Hummel observed that 1% of male mice strain 129 developed testicular teratomas extensive research for characterization and for understanding the properties of EC cells was carried out. Around 1970 the first cell cultures of EC cells were reported. A lot of EC cells lines came into existence which could be maintained in an undifferentiated form in-vitro and formed teratomas when transplanted back to the appropriate host. EC cells are pluripotent but sometimes they loose this ability and then are termed as nullipotent. The mouse fibroblast layer was used to maintain the undifferentiated state of EC cells and STO line of transformed mouse fibroblast became the standard feeder layer. By early 1960-70 specific antisera were developed for specific surface antigens that proved that EC and ICM cells express same type of cell surface antigen thus concreting the fact that EC cells are similar to stem cells found in blastocyst. With the advent of monoclonal antibodies a specific antigen common to both was found which is known as stage-specific embryonic antigen 1 (SSEA 1). Various experiments also led to the identification of 2 new antigens SSEA3 and SSEA 4. Many experiments were carried out to confirm that EC cells are indeed the counterpart of ICM cells. In one experiment by Brinster (1974) small population of EC cells from agouti mouse was transplanted back into a blastocyst from an albino strain. The progeny has patches of agouti fur along with albino fur indicating that some fur developed from the implanted EC cells. Experiments proved that retinoic acid was capable of inducing differentiation in a number of EC cell lines; the most common example is the P19 cell line which differentiates into neuronal direction when exposed to retinoic acid but is driven towards the mesodermal direction with formation of muscle cells when exposed to DMSO (dimethylsulfoxide). Other inducing agents like hexamethylene bisaccetamide (HMBA) also affect EC cell lines.
Studying mouse EC cells lines is of a less hassle as compared to Human EC cells lines since there are lot of ethical barriers to be considered however significant amount of research has been carried out in this filed. Human EC cell lines were first derived from human GCT and maintained as xenografts but later many other cell lines were established in cultures for e.g. TERA 1, TERA 2 and SuSa. Human EC cells undergo morphological changes accompanied by changes in expression of different surface markers depending on the culture conditions. A large flat phenotype is observed with expression of SSEA 1 when cultured at low culture densities. Many cell lines require a feeder layer to prevent differentiation. The most extensively studied is the TERA2 line.
Teratocarcinomas were not studied in detail till 1957 but when Stevens and Hummel observed that 1% of male mice strain 129 developed testicular teratomas extensive research for characterization and for understanding the properties of EC cells was carried out. Around 1970 the first cell cultures of EC cells were reported. A lot of EC cells lines came into existence which could be maintained in an undifferentiated form in-vitro and formed teratomas when transplanted back to the appropriate host. EC cells are pluripotent but sometimes they loose this ability and then are termed as nullipotent. The mouse fibroblast layer was used to maintain the undifferentiated state of EC cells and STO line of transformed mouse fibroblast became the standard feeder layer. By early 1960-70 specific antisera were developed for specific surface antigens that proved that EC and ICM cells express same type of cell surface antigen thus concreting the fact that EC cells are similar to stem cells found in blastocyst. With the advent of monoclonal antibodies a specific antigen common to both was found which is known as stage-specific embryonic antigen 1 (SSEA 1). Various experiments also led to the identification of 2 new antigens SSEA3 and SSEA 4. Many experiments were carried out to confirm that EC cells are indeed the counterpart of ICM cells. In one experiment by Brinster (1974) small population of EC cells from agouti mouse was transplanted back into a blastocyst from an albino strain. The progeny has patches of agouti fur along with albino fur indicating that some fur developed from the implanted EC cells. Experiments proved that retinoic acid was capable of inducing differentiation in a number of EC cell lines; the most common example is the P19 cell line which differentiates into neuronal direction when exposed to retinoic acid but is driven towards the mesodermal direction with formation of muscle cells when exposed to DMSO (dimethylsulfoxide). Other inducing agents like hexamethylene bisaccetamide (HMBA) also affect EC cell lines.
Studying mouse EC cells lines is of a less hassle as compared to Human EC cells lines since there are lot of ethical barriers to be considered however significant amount of research has been carried out in this filed. Human EC cell lines were first derived from human GCT and maintained as xenografts but later many other cell lines were established in cultures for e.g. TERA 1, TERA 2 and SuSa. Human EC cells undergo morphological changes accompanied by changes in expression of different surface markers depending on the culture conditions. A large flat phenotype is observed with expression of SSEA 1 when cultured at low culture densities. Many cell lines require a feeder layer to prevent differentiation. The most extensively studied is the TERA2 line.
Reference: - Stem Cell Biology (chapter 11 Embryonal Carcinoma Cells as Embryonic stem cells by Peter Andrews, Stefan Przyborski and James Thomson).
