Tumour regulation of fibroblast hyaluronan expression: a mechanism to facilitate tumour growth and invasion
Tumour regulation of fibroblast hyaluronan expression: a mechanism to facilitate tumour growth and invasion
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DOI：
10.1093/carcin/bgi064
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发表时间：
2005-07-01
期刊：
影响因子：
4.7
通讯作者：
Tammi, RH
中科院分区：
文献类型：
--
作者：
Edward, M;Gillan, C;Tammi, RH
透明质酸是一种高分子量的糖胺聚糖，与细胞增殖和迁移有关。在许多不同类型的肿瘤中，肿瘤进展与透明质酸的产生密切相关，无论是肿瘤细胞还是周围的基质细胞。我们研究了侵袭性黑色素瘤细胞系（C8161）刺激成纤维细胞透明质酸合成的能力，以及细胞表面CD44受体和透明质酸与侵袭的关系。在低糖培养基（1 mg/ml）中制备的黑色素瘤细胞条件培养基（CM）刺激了成纤维细胞糖胺聚糖的合成，通过[H-3]葡萄糖胺结合测定，透明质酸的合成通过特定的透明质酸结合板测定，而在高糖培养基（4.5 mg/ml）中制备的肿瘤细胞条件培养基（CM）抑制了成纤维细胞糖胺聚糖的合成。高糖肿瘤细胞cm含有大量的乳酸，似乎可以抑制肿瘤源性因子对成纤维细胞糖胺聚糖合成的刺激，因为乳酸的去除恢复了刺激活性。黑色素瘤细胞播撒在收缩的胶原晶格上，在空气/液体界面孵育，在表面迅速形成多层细胞团，凝胶明显浸润。胶原凝胶内可见透明质酸染色，侵袭的肿瘤细胞周围可见强染色，但靠近表面的细胞层周围没有。CD44在肿瘤细胞上的表达仅限于入侵细胞，并与细胞透明质酸染色相对应。肿瘤细胞侵入无成纤维细胞的胶原晶格周围和之间的透明质酸染色也很明显。单层培养的C8161细胞CD44染色强烈，但透明质酸染色的细胞很少，同时没有检测到透明质酸释放到培养基中。综上所述，C8161黑色素瘤细胞刺激了成纤维细胞透明质酸的合成，而在胶原晶格中，无论成纤维细胞存在与否，只有侵袭性肿瘤细胞表达CD44和透明质酸。
Hyaluronan, a high molecular weight glycosaminoglycan is associated with cellular proliferation and migration. In a number of different tumour types, there is a close correlation between tumour progression and hyaluronan production, either by the tumour cells or the surrounding stromal cells. We have examined the ability of an aggressive melanoma cell line (C8161) to stimulate the synthesis of fibroblast hyaluronan, and the association of cell-surface CD44 receptors and hyaluronan with invasion. Melanoma cell-conditioned medium (CM) prepared in low glucose medium (1 mg/ml) stimulated the synthesis of fibroblast glycosaminoglycan as measured by [H-3] glucosamine incorporation, and the synthesis of hyaluronan as measured using a specific hyaluronan-binding plate assay, while tumour cell-CM prepared in high glucose medium (4.5 mg/ml) inhibited the synthesis of fibroblast glycosaminoglycan. High glucose tumour cell-CM contained large amounts of lactate that appeared to inhibit the tumour-derived factor stimulation of fibroblast glycosaminoglycan synthesis, as removal of the lactate restored the stimulating activity. Melanoma cells seeded on contracted collagen lattices and incubated at the air/liquid interface rapidly formed a multilayered cell mass on the surface, with significant invasion of the gel. Hyaluronan staining was apparent within the collagen gel, and strong staining was seen around the invading tumour cells, but not around those cell layers near the surface. CD44 expression on the tumour cells was confined to those invading cells and corresponded to cellular hyaluronan staining. Hyaluronan staining was also apparent around and between tumour cells invading fibroblast-free collagen lattices. Monolayer cultures of C8161 cells stained strongly for CD44, but few cells stained for hyaluronan, while no detectable hyaluronan was released into the medium. In summary, the C8161 melanoma cells stimulated the synthesis of fibroblast hyaluronan, and in collagen lattices, Only the invasive tumour cells expressed CD44 and hyaluronan, either in the presence or absence of fibroblasts.