一种新的~6 kDa HA分子在结肠癌转移中的作用及机制研究

细胞外基质（ECM）重塑是影响肿瘤转移的关键因素。透明质酸（HA）是ECM主要成分，肿瘤发生时合成及降解增多，导致低分子量HA（LMW-HA）异常累积。肿瘤微环境中异常LMW-HA的分子量尚不明确，其在肿瘤进展中的作用也存在争议。本课题前期发现：① 结肠癌患者癌组织中LMW-HA表达显著高于癌旁组织；② 结肠癌相关LMW-HA分子量主要集中在~6 kDa；③结肠癌患者组织及血清~6 kDa HA（HA6）水平与肿瘤转移相关，提示肿瘤微环境中~6 kDa HA 可能参与了结肠癌转移。本研究首次探讨结肠癌相关HA6在肿瘤转移中的作用及机制。内容：① 明确肿瘤微环境来源HA6 在结肠癌转移中的作用；② 探索HA6-CD44相互作用参与结肠癌转移的具体机制，以期从新视角揭示结肠癌转移机制。

Extracellular matrix (ECM) remodeling is the key factor influencing tumor metastasis. Hyaluronan (HA), a major component of ECM, is increasingly synthesized and degraded during tumorigenesis, leading to the abnormal accumulation of low molecular weight HA (LMW-HA). The molecular weight of abnormal LMW-HA in tumor microenvironment is unclear, and its role in tumor progression remains disputed. Previous work from our laboratory showed that: (1) LMW-HA levels were increasingly expressed in cancer tissues than that in matched noncancerous tissues from patients with colorectal cancer (CRC); (2) The molecular weight of CRC associated LMW-HA mainly focused in ~ 6 kDa; (3) ~6 kDa HA (HA6) levels in cancer tissues and sera from CRC patients are associated with tumor metastasis, suggesting that ~6 kDa HA in tumor microenvironment may be involved in CRC metastasis. For the first time, this project aim to explore the role of CRC associated HA6 in tumor metastasis and the underlying mechanisms. Contents: (1) Clarify the effects of HA6 derived from tumor microenvironment in CRC metastasis; (2) Study the role of HA6-CD44 interaction in CRC metastasis and the mechanisms involved. Our project may provide a new insight to elucidate the mechanism of CRC metastasis.