1 1 . M U C O P O L Y S A C C H A R I D E S IN T I S S U E C U L T U R E
383
H . A C T I O N OF V I T A M I N S A N D H O R M O N E S O N
M U C O P O L Y S A C C H A R I D E B I O S Y N T H E S I S A N D T U R N O V E R
This subject is discussed in detail by Fell elsewhere in this volume
(Chapter 17), and only those aspects of particular relevance to the
present theme are considered here.
Fell and Mellanby (1952) reported that when embryonic cartilage
is grown in a medium containing excess vitamin A the most conspicuous
effect is the disappearance of metachromatic material from the matrix.
Dingle et al. (1961) found these changes to be associated with a 5 0 %
loss of amino sugars. Thus, the contents of galactosamine and glucosamine were respectively 14 /xg and 2-9 ^g/bone in the control explants
and 6-25 /xg and 1-9 /xg/bone in the vitamin A treated explants. This
decrease in total hexosamine content in the vitamin treated rudiments
was accompanied by quantitatively similar decreases in the wet and
dry weights. These changes were not due simply to the presence of
fewer cells in the treated explants, since the ratio of dry weight/DNA
in the latter was much lower than in the controls, but to the release
tional type, which produced hyaluronic acid and were identified as
fibroblasts derived from the host's subcutaneous tissue in response to
implantation of the tumour. Extracts prepared from larger Walker
tumours were found to depolymerize the hyaluronic acid present in
both embryo extract and in cultures that contained the fibroblasts. The
production of hyaluronidase is not considered to be an acquired
property of these tumour cells, but to pre-exist in the normal stem cells
of carcinomas. Grossfeld (1961) points out that many malignant
tumours, especially sarcomas, do not produce hyaluronidase. It seems
likely that the invasiveness of these tumours is not due to the destruction
ofthe mucopolysaccharides of connective tissue, but to the hydrolysis of
the protein component ofthe mucoprotein by proteolytic enzymes. Not
all "spreading factors" are hyaluronidase-like enzymes (Duran-Reynals,
1950). Histological studies, for example, indicate that proteolytic
enzymes destroy the ground substance more rapidly than does hyaluronidase (Gersh and Catchpole, 1949; Day, 1949). The secretion of
proteolytic enzymes by the tumour tissue might explain why large
amounts of hyaluronic acid are often found to be associated with
tumours of this type. Such an accumulation of mucopolysaccharides
in response to proteolytic digestion has a parallel in the previously
described events that occur in organ cultures of embryonic bone
rudiments under the influence of vitamin A, papain and lysosomal
enzymes.
383
H . A C T I O N OF V I T A M I N S A N D H O R M O N E S O N
M U C O P O L Y S A C C H A R I D E B I O S Y N T H E S I S A N D T U R N O V E R
This subject is discussed in detail by Fell elsewhere in this volume
(Chapter 17), and only those aspects of particular relevance to the
present theme are considered here.
Fell and Mellanby (1952) reported that when embryonic cartilage
is grown in a medium containing excess vitamin A the most conspicuous
effect is the disappearance of metachromatic material from the matrix.
Dingle et al. (1961) found these changes to be associated with a 5 0 %
loss of amino sugars. Thus, the contents of galactosamine and glucosamine were respectively 14 /xg and 2-9 ^g/bone in the control explants
and 6-25 /xg and 1-9 /xg/bone in the vitamin A treated explants. This
decrease in total hexosamine content in the vitamin treated rudiments
was accompanied by quantitatively similar decreases in the wet and
dry weights. These changes were not due simply to the presence of
fewer cells in the treated explants, since the ratio of dry weight/DNA
in the latter was much lower than in the controls, but to the release
tional type, which produced hyaluronic acid and were identified as
fibroblasts derived from the host's subcutaneous tissue in response to
implantation of the tumour. Extracts prepared from larger Walker
tumours were found to depolymerize the hyaluronic acid present in
both embryo extract and in cultures that contained the fibroblasts. The
production of hyaluronidase is not considered to be an acquired
property of these tumour cells, but to pre-exist in the normal stem cells
of carcinomas. Grossfeld (1961) points out that many malignant
tumours, especially sarcomas, do not produce hyaluronidase. It seems
likely that the invasiveness of these tumours is not due to the destruction
ofthe mucopolysaccharides of connective tissue, but to the hydrolysis of
the protein component ofthe mucoprotein by proteolytic enzymes. Not
all "spreading factors" are hyaluronidase-like enzymes (Duran-Reynals,
1950). Histological studies, for example, indicate that proteolytic
enzymes destroy the ground substance more rapidly than does hyaluronidase (Gersh and Catchpole, 1949; Day, 1949). The secretion of
proteolytic enzymes by the tumour tissue might explain why large
amounts of hyaluronic acid are often found to be associated with
tumours of this type. Such an accumulation of mucopolysaccharides
in response to proteolytic digestion has a parallel in the previously
described events that occur in organ cultures of embryonic bone
rudiments under the influence of vitamin A, papain and lysosomal
enzymes.