Human cancer cell lines A431 and MCF7, which do not produce tenascin (TN) in vitro, were found to produce TN when injected into nude mice or co-cultured with the embryonic mesenchyme. The TN expression in the developing A431 solid tumor was demonstrated by immunohistochemistry and by in situ hybridization. Human TN was detected in culture media by western blot analysis using human specific monoclonal antibody (RCB-1). During tumorigenesis, in the early stage, mouse TN was actively induced and deposited in the peri- and intertumor spaces surrounding the developing tumor. Two days later, TN derived from human epithelial cancer cells was induced and mainly deposited in the intertumor basement membrane. After this stage, tumor cells were actively producing TN. On the other hand, TN induction in non TN-producing cells, such as A431 and MCF7 cell lines, was also observed in vitro. Although cell lines such as NIH-3T3, phi 2, STO, 2H6, 3E5 and CMT315, had no effect on the TN induction, primary cultured embryonic mesenchyme effectively stimulated the TN expression in the cancer cell lines. This mesenchymal effect decreased with age and was entirely lost postnatally. Furthermore, conditioned media from these embryonic mesenchymes could reproduce the same effects on TN induction as observed in the co-culture study. In conclusion, these findings suggest that TN induction in epithelial cancer cells may depend on interactions with the surrounding environment, that these interactions may be mediated by a soluble factor(s) derived from the surrounding mesenchyme and that the TN induction observed in the tumorigenesis may reflect histogenesis during the embryonic period.

REFERENCES

Aufderheide
E.
,
Chiquet-Ehrismann
R.
,
Ekblom
P.
(
1987
).
Epithelial-mesenchymal interactions in the developing kidney lead to expression of tenascin in mesenchyme.
J. Cell Biol.
105
,
599
608
Aufderheide
E.
,
Ekblom
P.
(
1988
).
Tenascin during gut development: appearance in the mesenchyme shift in molecular forms, and dependence on epithelial-mesenchymal interactions.
J. Cell Biol.
105
,
2341
2349
Bourdon
M. A.
,
Wikstrand
C. J.
,
Furthmaryr
H.
,
Matthews
T. J.
,
Bigner
D. D.
(
1983
).
Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody.
Cancer Res.
43
,
2796
2805
Chiquet-Ehrismann
R.
(
1990
).
What distinguishes tenascin from fibronectin?
FASEB J.
4
,
2598
2604
Chiquet-Ehrismann
R.
,
Mackie
E. J.
,
Pearson
C. A.
,
Sakakura
T.
(
1986
).
Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis.
Cell
47
,
131
139
Chiquet-Ehrismann
R.
,
Kalla
P.
,
Pearson
C. A.
,
Beck
K.
,
Chiquet
M.
(
1988
).
Tenascin interferences with fibronectin action.
Cell
53
,
383
390
Daniloff
J. K.
,
Crossin
K. L.
,
Pincon-Raymond
M.
,
Murawsky
M.
,
Rieger
F.
,
Edelman
G. M.
(
1989
).
Expression of cytotactin in the normal and regenerating nueromuscular system.
J. Cell Biol.
108
,
625
635
Friedlander
D. R.
,
Hoffman
S.
,
Edelman
G. M.
(
1988
).
Functional mapping of cytotactin: proteolytic fragments active in cell-substrate adhesion.
J. Cell Biol.
107
,
2329
2340
Herlyn
M.
,
Graevev
U.
,
Speicher
D.
,
Sela
B. A.
,
Bennicelli
J. L.
,
Kath
R.
,
Guerry
I. V. D.
(
1991
).
Characterization of tenascin secreted by human melanoma cells.
Cancer Res.
51
,
4853
4858
Inaguma
Y.
,
Kusakabe
M.
,
Mackie
E. J.
,
Pearson
C. A.
,
Chiquet-Ehrismann
R.
,
Sakakura
T.
(
1988
).
Epithelial induction of stromal tenascin in the mouse mammary gland: from embryogenesis to carcinogenesis.
Dev. Biol.
128
,
245
255
Jones
F. S.
,
Hahhman
S.
,
Cunningham
B. A.
,
Edelman
G. M.
(
1989
).
A detailed structural model of cytotactin: protein, homologies, alternative RNA splicing and binding regions.
Proc. Nat. Acad. Sci. USA
86
,
1905
1909
Koch
M.
,
Wehrle-Haller
B.
,
Baumgartner
S.
,
Spring
J.
,
Brubacher
D.
,
Chiquet
M.
(
1991
).
Epithelial synthesis of tenascin at tips of growing bronchi and graded accummulation in basement membrane and mesenchyme.
Exp. Cell Res.
194
,
297
300
Kusakabe
M.
,
Yokoyama
M.
,
Sakakura
T.
,
Nomura
T.
,
Hosick
H. L.
,
Nishizuka
Y.
(
1988
).
A novel methodology for analysis of cell distribution in chimeric mouse organs using a strain specific antibody.
J. Cell Biol.
107
,
257
265
Laemmli
U. K.
(
1970
).
Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
Nature
227
,
680
685
Mackie
E. J.
,
Halfter
W.
,
Liverani
D.
(
1988
).
Induction of tenascin in healing wounds.
J. Cell Biol.
107
,
2757
2767
Mackie
E. J.
,
Chiquet-Ehrismann
R.
,
Pearson
C. A.
,
Inaguma
Y.
,
Taya
K.
,
Kawarada
Y.
,
Sakakura
T.
(
1989
).
Tenascin is a stromal marker for epithelial malignancy in the mammary gland.
Proc. Nat. Acad. Sci. USA
84
,
4621
4625
Natali
P. G.
,
Nicotra
M. R.
,
Bortolazzi
A.
,
Mottolese
M.
,
Coscia
N.
,
Bigotti
A.
,
Zardi
L.
(
1990
).
Expression and production of tenascin in benign and malignant lesions of melanocyte lineage.
Int. J. Cancer.
46
,
586
590
Nies
D. E.
,
Hemesath
T. J.
,
Kim
J. H.
,
Gulcher
J. R.
,
Stefansson
K.
(
1991
).
The complete cDNA sequence of human hexabrachion(tenascin).
J. Biol. Chem.
266
,
2818
2823
Nishi
T.
,
Weinstein
J.
,
Gillespie
W. M.
,
Paulson
J. C.
(
1991
).
Complete primary structure of porcine tenascin.
Eur. J. Biochem.
202
,
643
648
Oike
Y.
,
Hiraiwa
H.
,
Kawakatsu
H.
,
Nishikai
M.
,
Okinaka
T.
,
Suzuki
T.
,
Okada
A.
,
Yatani
R.
,
Sakakura
T.
(
1990
).
Isolation and characterization of human fibroblast tenascin. An extracellular matrix glycoprotein of interest for developmental studies.
Int. J. Dev. Biol.
34
,
309
317
Pearson
C. A.
,
Pearson
D.
,
Shibahara
S.
,
Hofsteenge
J.
,
Chiquet-Ehrismann
R.
(
1988
).
Tenascin: cDNA cloning and induction by TGF-β.
EMBO J.
7
,
2977
2981
Sakakura
T.
,
Kusano
I.
,
Kusakabe
M.
,
Inaguma
Y.
,
Nishizuka
Y.
(
1987
).
Biology of mammary fat pad in fetal mouse: capacity to support development of various fetal epithelia in vivo.
Development
100
,
421
430
Sakakura
T.
,
Kusano
I.
(
1991
).
Tenascin in tissue perturbation repair.
Acta Pathologica Japonica
41
,
247
258
Saga
Y.
,
Tsukamoto
T.
,
Jing
N.
,
Kusakabe
M.
,
Sakakura
T.
(
1991
).
Mouse tenascin: cDNA cloning structure and temporal expression of isoforms.
Gene
104
,
177
185
Siri
A.
,
Carnemolla
B.
,
Saginati
M.
,
Leprini
A.
,
Casari
G.
,
Baralle
F.
,
Zardi
L.
(
1991
).
Human tenascin: primary structure, pre-mRNA splicing patterns and localization of the epitopes recognized by two monoclonal antibodies.
Nucl. Acid Res.
19
,
525
531
Tucker
R. P.
(
1991
).
The sequential expression of tenascin mRNA in epithelium and mesenchyme during feather morphogenesis.
Roux's Arch. Dev. Biol.
200
,
108
112
Tucker
R. P.
,
McKay
S.E.
(
1991
).
The expression of tenascin by neural crest and glia.
Development
112
,
1031
1039
Tsukamoto
T.
,
Kusakabe
M.
,
Saga
Y.
(
1991
).
In situ hybridization with non-radioactive digoxigenin-11-UTP-labeled cRNA probes: localization of developmentally regulated mouse tenascin mRNAs.
Int. J. Dev. Biol.
35
,
25
32
Vainio
S.
,
Jalkanen
M.
,
Thesleff
I.
(
1989
).
Syndecan and tenascin expression is inducted by epithelial-mesenchymal interactions in embryonic tooth mesenchyme.
J. Cell Biol.
108
,
1945
1954
Weller
A.
,
Beck
S.
,
Ekblom
P.
(
1991
).
Amino acid sequence of mouse tenascin and differential expression of two tenascin isoforms during embryogenesis.
J. Cell Biol.
112
,
355
362
Whitby
D. J.
,
Ferguson
M. W. J.
(
1991
).
The extracellular matrix of lipwounds in fetal, neonatal and adult mice.
Development
112
,
538
587
This content is only available via PDF.