Protein Collagen VII and Cancer
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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