Disease relevance of TACSTD2

• The abnormal transcription of TACSTD2 and S100A2 are thought to be unique molecular markers of the preinvasive stage of lung adenocarcinoma [1].
• The frequency of TACSTD2 positivity was increased in 16 of 22 bronchioloalveolar carcinomas (BAC) and adenocarcinoma with mixed subtype with BAC component (mixed BAC) [1].
• Defined by monoclonal antibody GA733, the GA733-2 antigen is a cell surface 40-kDa glycoprotein associated with human carcinomas of various origins [2].
• BACKGROUND: The gastrointestinal carcinoma antigen GA733 is a potential target for passive and active immunotherapy for patients with colorectal carcinoma [3].
• We investigated the capacity of full-length CO17-1A/GA733 Ag expressing multiple potentially immunogenic epitopes and encoded by recombinant adenovirus 5 (Ad5 GA733-2) to induce humoral, cellular, and/or protective immunity in mice [4].

High impact information on TACSTD2

• Colorectal carcinoma invasion inhibition by CO17-1A/GA733 antigen and its murine homologue [3].
• The availability of a murine homologue of GA733, i.e., murine epithelial glycoprotein (mEGP), allows for functional analysis of cell adhesion as it relates to tumor growth and invasion, both in vitro and in vivo [3].
• GA733- or mEGP-producing cells were evaluated for homophilic adhesion, growth on plastic surfaces, colony formation in soft agar, and invasion through a reconstructed basement membrane (Matrigel). mEGP-producing cells were also examined for their capacity to metastasize in mice [3].
• The positions of 12 cysteine residues in the extracellular domains of the two GA733 antigens are conserved, as is the overall distribution of hydrophobic and hydrophilic residues [2].
• The monoclonal antibody-defined, tumor-associated antigen GA733 was purified from the SW948 human colorectal carcinoma cell line and its partial amino acid sequence was determined [5].

Chemical compound and disease context of TACSTD2

• Two internalizing mAbs, LL2 (anti-CD 22 B-cell lymphoma mAb) and RS7 (an anti-adenocarcinoma mAb which targets EGP-1 antigen), labeled with this procedure exhibited a 2-3-fold better cellular retention in Ramos and Calu-3 tumor cell lines, in vitro, respectively, compared to the same mAbs radioiodinated with the chloramine-T method [6].

Biological context of TACSTD2

• PURPOSE: To report a novel missense mutation in TACSTD2 gene, L186P, responsible for gelatinous droplike dystrophy (GDLD) [7].
• The results confirm that the missense mutation L186P in the TACSTD2 gene is also responsible for the GDLD phenotype [7].
• The amino acid sequence derived from the previously described GA733-related gene, GA733-1, was found to be 49% identical to GA733-2 [2].
• The cytoplasmic tail of Trop-2 possesses potential serine and tyrosine phosphorylation sites and a phosphatidyl-inositol binding consensus sequence [8].
• Full-length native GA733 protein was isolated from human tumor cells, and the extracellular domain protein (GA733-2E) was isolated from supernatants of recombinant baculovirus-infected insect cells by immunoaffinity chromatography [9].

Anatomical context of TACSTD2

• A 1.1-kb DNA fragment of the TACSTD2 gene was amplified and analyzed using a molecular biological method. cDNA from the patient's cornea was also analyzed to determine which allele was expressed in the patient's corneal epithelium [7].
• Trop-1 and Trop-2 appear to be specifically expressed on syncytio- and cytotrophoblasts, whereas Trop-3 and Trop-4 are also detected on various tumor cell lines, normal lymphocytes, and monocytes [10].
• The sequence of the epithelial glycoprotein antigen is identical to the cell membrane protein recognized by the monoclonal antibody KS 1/4 and is homologous to the tumor-associated antigen GA733 [11].
• Immunohistoperoxidase staining with polyclonal rabbit antibodies to the human antigen revealed the human homologue on normal small intestine, colon and liver of mice, rats and non-human primates, whereas mouse monoclonal antibodies to the CO17-1A or GA733 epitopes on the human antigen did not detect the antigen [12].
• Chimeric T cell receptors were constructed by ligating single-chain genes of either of two EGP40-specific monoclonal antibodies (CO17.1 A, GA733) to the Fc receptor gamma-signaling chain [13].

Associations of TACSTD2 with chemical compounds

• We propose to call the antigen detected by SCLC-cluster-2 antibodies "epithelial glycoprotein 2" (EGP-2), and the epithelium-associated glycoprotein recognized by antibodies clustered in SCLC cluster 13 (see elsewhere in this volume) "epithelial glycoprotein 1" (EGP-1) [14].
• Very close to the location where the mutation was identified in the M1S1 gene, a single-nucleotide polymorphism (518A/C) was found, changing aspartic acid to alanine at codon 173 [15].
• The rate constant for carbon monoxide binding to this form of hemoglobin is 4.1 X 10(6) M-1 S-1 at 24 degrees in our solutions [16].
• The equilibrium constant for CO binding to the ferrous hemeprotein was measured to be 1.7 X 10(-5) M-1 and the CO association rate constant determined to be 5.4 X 10(3) M-1 S-1 [17].
• The second order rate constant (Kf) for the formation of Compound X at pH 4.5 (optimum pH) is 0.9 X 10(6) M-1 S-1 [18].

Regulatory relationships of TACSTD2

• Ad5 GA733-2 induced Ag-specific Abs that reacted predominantly to CO17-1A- and GA733-unrelated epitopes on the Ag and lysed Ag-positive CRC targets in conjunction with effector cells [4].
• Kinetic analyses revealed that factor VII activation in the presence of relipidated tissue factor apoprotein can be defined by a second-order reaction mechanism in which factor VII is activated by factor VIIa with an apparent second-order rate constant of 7.2 x 10(3) M-1 S-1 [19].

Other interactions of TACSTD2

• The high transcription of TACSTD2 and S100A2 in PL16T was confirmed by in situ hybridization [1].
• Trop-1 and Trop-2 are homologous to serum IGF-II-binding proteins and appear as signal transducers [20].
• Mutagenesis of the TROP2 and CCND1 sequences and in vitro transcription/translation show that a cryptic promoter is present in the 3' coding region of CCND1 [21].
• Targets on pancreatic cancer cells currently under investigation are mucins (MUC-1), glycoproteins (GA733), ras peptides and EGFRs [22].
• A novel TACSTD2 gene mutation in a Turkish family with a gelatinous drop-like corneal dystrophy [23].

Analytical, diagnostic and therapeutic context of TACSTD2

• Our findings indicate a close relationship between the C215 antigen and other members of the GA-733 family, some of which are currently being used as targets in clinical trials with monoclonal antibodies [24].
• METHODS: EpCAM reactivity was evaluated by immunohistochemistry in 43 retinoblastoma specimens from 43 patients, by using the monoclonal antibody GA733 [25].
• These results have important implications for experimental active and passive immunotherapy targeting the CO17-1A/GA733 antigen [12].
• METHODS: DNA was extracted from leukocytes of peripheral blood of the two affected members of the family and from controls, and the coding region of M1S1 was amplified by polymerase chain reaction (PCR) [26].
• Polyclonal goat anti-idiotypic Abs directed against anti-human gastrointestinal carcinoma mAb GA733 were administered to 13 colon cancer patients who had their primary tumor and lymph node metastases removed before immunotherapy [27].

References