Protein Collagen VII and Cancer
updated on April 19, 2007
In normal tissues, Protein Collagen VII is present mainly
in the basement membrane surrounding or underlying
combined epithelia, such as those lining breast, prostate,
and bronchus, and stratified epithelia, such as larynx,
esophagus, trachea, vagina, and epidermis.

And, Protein Collagen VII usually is absent in the "simple'
epithelia lining the major part of the gastrointestinal tract
(GI) tract, such as liver, stomach, and intestine, or around
blood vessels, muscle, and nerve fibers.

In late 1980s, scientists already observed that Protein
Collagen VII might be linked with certain types of cancers:

Jones JC et al, Northwest University noticed collagen VII
localized to the basement membrane zone of tumor cells in the
absence of the cytoplasmic constituents of hemidesmosomes
[1]. Pfaltz M. et al, University Hospital, Zurich, Switzerland,
found Type VII collagen is a component of cylindroma
basement membrane zone using immunofluorescence
technology [2]. Bruckner-Tuderman L. et al, University Hospital,
Zurich, Switzerland, suggested that human cylindroma is an
abundant source to produce collagen VII [3].

Wetzels et al, University Hospital, The Netherlands, studied the
distribution patterns of type VII collagen in normal and
malignant human tissues and concluded that invasive and
metastatic tumors do not express extensively type VII collagen
in general. However, exceptions to this rule exist in bladder
cancer, squamous carcinomas of the lung, tumors of the head
and neck region, female genital tract tumors, and in some
adenocarcinomas of the breast [4].

OTHER OBSERVATIONS

PROSTATE Immunohistochemical studies of prostate
carcinoma reveal that most primary carcinomas, including
high-grade tumors, are surrounded by a basal lamina
composed of laminin, type IV collagen, and entactin. [5] The
major components of the basal lamina surrounding normal
acini were laminin, type IV collagen, entactin, and type VII
collagen with variable amounts of tenascin. The basal lamina of
neoplastic acini had a similar composition, except for the loss
of type VII collagen, which was observed in all grades of
carcinoma. [7]

BLADDER In invasive bladder cancers, the majority showed
either loss of alpha 6 beta 4 and/or collagen VII expression or
showed a lack of co-localization of alpha 6 beta 4 and collagen
VII. [6]

NERVOUS SYSTEM Scattered abnormal vessels showed
neo-expression of type VII collagen in about half of the
astrocytic and ependymal tumours. Anchoring fibrils or at least
epitopes of their major structural component are present in
normal and pathological cerebral structures, indicating a
unique distribution of type VII collagen in the nervous system. [8]

SKIN Type VII collagen retained a more linear, continuous and
uniform distribution in the areas of progressed epithelial
dysplasia. All invasive carcinomas were characterized by a BL
which was disrupted by gaps of varying size but, again,
showed a more uniform and less discontinuous distribution of
the anchoring molecule type VII collagen. [9]

POSSIBLE APPLICATIONS

Khavari and his group at Standard University deduced that
collagen VII protein fragment might be necessary to allow
cancer to form. They proved this by adding the collagen VII
protein fragment to recessive dystrophic epidermolysis bullosa
cells that lacked it-an intervention that restored cancer-forming
ability.
The group further blocked that protein fragment using an
antibody and tried to induce the normal skin cells to become
cancerous. But, they failed. Without that fragment, the cancer
could not spread. [10]

Further proof came from work in animal studies. The group
treated the mice with the collagen VII-blocking antibody, the
skin cancer failed to spread, though the cancer remained.
Consequently, this cancer isn't deadly unless it spreads.

REFERENCES

[1] Jones JC et al, Hemidesmosomes, collagen VII, and intermediate filaments in basal cell
carcinoma, J Invest Dermatol. 1989 Nov;93(5):662-71.

[2] Pfaltz M. et al, Type VII collagen is a component of cylindroma basement membrane
zone, J Cutan Pathol. 1989 Dec;16(6):388-95.

[3] Bruckner-Tuderman L et al, Cylindroma overexpresses collagen VII, the major anchoring
fibril protein, J Invest Dermatol. 1991 May;96(5):729-34.

[4]  Wetzels RH et al, Distribution patterns of type VII collagen in normal and malignant
human tissues, Am J Pathol. 1991 Aug;139(2):451-9.

[5] Nagle RB et al, Adhesion molecules, extracellular matrix, and proteases in prostate
carcinoma, J Cell Biochem Suppl. 1994;19:232-7.

[6] Liebert M et al, Loss of co-localization of alpha 6 beta 4 integrin and collagen VII in
bladder cancer, Am J Pathol. 1994 Apr;144(4):787-95.

[7] Knox JD et al, Deferential expression of extracellular matrix molecules and the alpha
6-integrins in the normal and neoplastic prostate, Am J Pathol. 1994 Jul;145(1):167-74.

[8] Paulus W et al, Expression of type VII collagen, the major anchoring fibril component, in
normal and neoplastic human nervous system. Virchows Arch. 1995;426(2):199-202.

[9] Kopf-Maier P et al, Behavior of the basement membrane during carcinoma cell invasion
in chemically induced carcinomas of the skin, Acta Anat (Basel). 1996;155(1):1-13

[10] Protein that helps skin cancer spread identified by Stanford researchers, Newswire,
2005-03-18, Science, March 18, 2005.
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