Synthesis and protein distribution of the unspliced large tenascin-C isoform in oral squamous cell carcinoma.
The inclusion or omission of the alternatively spliced region in the tenascin-C (Tn-C) mRNA gives rise to the large (Tn-C(L)) or small (Tn-C(S)) variant, respectively. Tn-C(L) is thought to be a typical component of provisional extracellular matrices (ECMs) and is expressed during tumour stroma remodelling. Tn-C(L) synthesis has been studied using RNA/RNA in situ hybridization, and Tn-C(L) protein distribution, using immunohistochemistry (clone BC-2), in 18 oral squamous cell carcinomas (OSCCs) of different grades of malignancy. While the Tn-C(L) protein was demonstrated within the whole stromal compartment regardless of grade of malignancy, the majority of the Tn-C(L) mRNA signal-bearing cells were carcinoma cells. Only a few stromal myofibroblasts were able to synthesize Tn-C(L), as revealed by alpha-smooth muscle actin double staining. In well-differentiated carcinomas (G1), the Tn-C(L) synthesizing carcinoma cells were localized as a single positive cell layer in the tumour stroma interface, particularly in invasive areas. A higher grade of malignancy (G2/G3) is associated with a significantly increased number of Tn-C(L) synthesizing carcinoma cells randomly distributed within the invading tumour areas. Double-staining experiments (Tn-C(L) mRNA ISH/BC-2 immunohistochemistry) indicate that these cells are capable of organizing and depositing a three-dimensional Tn-C(L) matrix. Even though an instructive and/or inductive role of the carcinoma cells in tumour stroma formation cannot be excluded, these results demonstrate that carcinoma cells can directly produce the ECM components of tumour stroma.
Hindermann
W
W
Institute of Pathology, Friedrich Schiller University, Jena, Germany.
Berndt
A
A
Borsi
L
L
Luo
X
X
Hyckel
P
P
Katenkamp
D
D
Kosmehl
H
H
D001485:Basement Membrane / Q000737:chemistry / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009061:Mouth Mucosa / Q000737:chemistry / Q000378:metabolism; D009062:Mouth Neoplasms / Q000737:chemistry / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000737:chemistry; D020033:Protein Isoforms / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000032:analysis; D018709:Statistics, Nonparametric; D019063:Tenascin / Q000096:biosynthesis* / Q000737:chemistry
D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012334:RNA, Neoplasm; D019063:Tenascin