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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