382
J. T . D I N G L E A N D M . W E B B
hydrolases to the metabolism of the cartilage cells, to their movement
within the matrix and to the turnover of connective tissue components
is a problem of great interest.
Apart from the action of papain and lysosomal protease, the only
other published work on the enzymic release of mucopolysaccharides
from organ cultures appears to be that of Paff and Seifter (1950).
These authors treated limb-bone rudiments from 6- to 9-day chick
embryos with hyaluronidase in culture for 6-12 days. At the end ofthe
experimental period the treated explants were smaller than the controls and the cartilage matrix much less basophilic. Since the basophilia of cartilage matrix is due in large part to the presence of chondroitin sulphate, the authors conclude that the change in the rudiments
was due to the hydrolysis of this mucopolysaccharide by the enzyme,
and suggest further that hyaluronidase may be important in the
removal of cartilage as observed in the process of endochondral bone
formation.
These studies on the action of added enzymes to tissues in culture
indicate possible in vitro methods for study of polysaccharide metabolism.
Since the addition of these enzymes does not apparently damage the
cell or impair its synthetic mechanisms and ability to undergo mitosis,
it should prove possible to degrade selectively the mucopolysaccharide
protein complexes in culture and to study the mechanism of resynthesis.
G . M U C O P O L Y S A C C H A R I D E B R E A K D O W N A N D I N V A S I V E
G R O W T H OF M A L I G N A N T T U M O U R S
After the discovery (Duran-Reynals, 1929) and characterization
(Chain and Duthrie, 1939, 1940) of the "spreading factors", several
investigators (e.g. Boyland and McClean, 1935; Duran-Reynals and
Stewart, 1931; Balazs and V o n Euler, 1952; Kabat, 1939; Pirie, 1942)
postulated an association between the secretion of enzymes of this type
and invasive growth of malignant tumours, without, however, direct
evidence that the malignant cells hydrolyse the mucopolysaccharide
components of the ground substance of adjacent connective tissues.
Recently, Grossfeld (1961) has studied the growth of the Walker
tumour 256, which originated from a mammary adenocarcinoma
of the rat, in vivo and in vitro, and has obtained evidence that a
hyaluronidase may contribute to the invasiveness of the tumour cells.
In vivo the growth of the Walker tumour is slow for the first 7 days after
subcutaneous transplantation, and then, after the destruction of the
barrier of connective tissue erected by the host, accelerates rapidly.
Cultures established from transplants after 4-7 days in vivo, in contrast
to those from older (10-16 days) tumours, contained cells of an addi-
J. T . D I N G L E A N D M . W E B B
hydrolases to the metabolism of the cartilage cells, to their movement
within the matrix and to the turnover of connective tissue components
is a problem of great interest.
Apart from the action of papain and lysosomal protease, the only
other published work on the enzymic release of mucopolysaccharides
from organ cultures appears to be that of Paff and Seifter (1950).
These authors treated limb-bone rudiments from 6- to 9-day chick
embryos with hyaluronidase in culture for 6-12 days. At the end ofthe
experimental period the treated explants were smaller than the controls and the cartilage matrix much less basophilic. Since the basophilia of cartilage matrix is due in large part to the presence of chondroitin sulphate, the authors conclude that the change in the rudiments
was due to the hydrolysis of this mucopolysaccharide by the enzyme,
and suggest further that hyaluronidase may be important in the
removal of cartilage as observed in the process of endochondral bone
formation.
These studies on the action of added enzymes to tissues in culture
indicate possible in vitro methods for study of polysaccharide metabolism.
Since the addition of these enzymes does not apparently damage the
cell or impair its synthetic mechanisms and ability to undergo mitosis,
it should prove possible to degrade selectively the mucopolysaccharide
protein complexes in culture and to study the mechanism of resynthesis.
G . M U C O P O L Y S A C C H A R I D E B R E A K D O W N A N D I N V A S I V E
G R O W T H OF M A L I G N A N T T U M O U R S
After the discovery (Duran-Reynals, 1929) and characterization
(Chain and Duthrie, 1939, 1940) of the "spreading factors", several
investigators (e.g. Boyland and McClean, 1935; Duran-Reynals and
Stewart, 1931; Balazs and V o n Euler, 1952; Kabat, 1939; Pirie, 1942)
postulated an association between the secretion of enzymes of this type
and invasive growth of malignant tumours, without, however, direct
evidence that the malignant cells hydrolyse the mucopolysaccharide
components of the ground substance of adjacent connective tissues.
Recently, Grossfeld (1961) has studied the growth of the Walker
tumour 256, which originated from a mammary adenocarcinoma
of the rat, in vivo and in vitro, and has obtained evidence that a
hyaluronidase may contribute to the invasiveness of the tumour cells.
In vivo the growth of the Walker tumour is slow for the first 7 days after
subcutaneous transplantation, and then, after the destruction of the
barrier of connective tissue erected by the host, accelerates rapidly.
Cultures established from transplants after 4-7 days in vivo, in contrast
to those from older (10-16 days) tumours, contained cells of an addi-