βIII-tubulin at the invasive margin of colorectal cancer: possible link to invasion

Abstract

Cell locomotion, including cancer cell invasion, is closely associated with the dynamics of cytoskeletal structures. Previous in vitro studies indicated that tubulin isotype composition may affect polymerization properties and dynamics of microtubules. Colorectal cancer is a good model for studying tumour invasion because of the easily detectable invasive front. Hence, we investigated the localization of beta(III)-tubulin in colorectal cancer specimens. Immunohistochemical staining for beta(III)-tubulin was evident in cancer cells apparently budding from adjacent malignant cells with a higher differentiation and negative staining. An association between beta(III)-tubulin immunoreactivity and tumour budding grade was demonstrated. To the best of our knowledge, this is the first report documenting a preferential localization of beta(III)-tubulin in the invading epithelium. From this finding arises the possibility that changes in tubulin isotypes could modulate the invading activity of cancer cells. Further investigations are needed to determine whether our findings have clinical implications.

Differential protein expression in primary breast cancer and matched axillary node metastasis

“…overexpression of β-tubulin in metastatic tumor suggests that metastasized tumor cells utilize microtubule functions, many of which involve in metastatic cascade. studies in other cancers also demonstrate invasive and metastatic roles of β-tubulin (25,26).…”

Invasive front of colorectal cancer: Dynamic interface ofpro-/anti-tumor factors

“…Previous studies on EMT and events occurring at the invasive tumor front implicate, in particular, the Wingless-INT (WNT) signalling pathway in the process of tumor budding evidenced by increased β-catenin immunohistochemical staining in tumor buds, a concomitant loss of E-cadherin and over-expression of laminin5γ2 along with activation of transcriptional repressors SLUG, and ZEB1 [22,23] . Overexpression of urokinase plasminogen activator receptor (uPAR), matrix metalloproteinase-7 and -9 (MMP7, MMP9), matrilysin, CD44, Ep-CAM, and extensive staining of β(Ⅲ)-tubulin, a major constituent of microtubules, have all been reported [20,[23][24][25][26][27][28][29][30] suggestive of the invasion and migration potential of tumor buds. Tumor buds seem to over-express CXCL12, a stromal cell-derived factor whose receptor CXC4 is involved in chemotaxis and angiogenesis [31] .…”

β_III-Тубулин — потенциальная мишень для подавления инвазивной активности злокачественных эпителиальных опухолей

“…Ðàíåå íàìè ïîêàçàíî, ÷òî â èíâàçèâíîì ôðîíòå êî-ëîðåêòàëüíîãî ðàêà ïîâûøåíà ýêñïðåññèÿ b III -òóáóëè-íà [9]. Çàòåì, ïðîâåäÿ ñðàâíåíèå ñ ýêñïðåññèåé b I -àöå-òèëèðîâàííîãî è òèðîçèíèðîâàííîãî a-òóáóëèíîâ, ìû óñòàíîâèëè, ÷òî èìåííî b III -òóáóëèí àññîöèèðîâàí ñ ôåíîìåíîì îïóõîëåâîãî ïî÷êîâàíèÿ, êîòîðûé, â ñâîþ î÷åðåäü, ïðåäñòàâëÿåò ñîáîé ïóë êëåòîê, íåïîñðåäñò-âåííî îñóùåñòâëÿþùèõ èíôèëüòðàòèâíûé ðîñò [1].…”

“… íåèçìåíåííûõ ýïèòåëèàëüíûõ êëåòêàõ òîëñòîé êèø-êè b III -òóáóëèí íå âñòðå÷àåòñÿ.  êëåòêàõ ðàêà òîëñòîé êèøêè ýêñïðåññèÿ äàííîé ìîëåêóëû ñêîíöåíòðèðîâà-íà â èíâàçèâíîì ôðîíòå îïóõîëè [9], ÷òî ìîaeåò ãîâî-ðèòü ëèáî î çíà÷åíèè b III -òóáóëèíà íåïîñðåäñòâåííî äëÿ èíâàçèâíîãî ðîñòà îïóõîëè, ëèáî î åãî ïðîòåêòîð-íîé ðîëè è çíà÷èìîñòè äëÿ âûaeèâàíèÿ ïóëà èíâàçèâ-íûõ êëåòîê.  ïîëüçó ïîñëåäíåãî ïðåäïîëîaeåíèÿ ãîâî-ðèò âûñîêàÿ óñòîé÷èâîñòü äàííîãî òèïà òóáóëèíà ê ñâîáîäíî-ðàäèêàëüíîìó ñòðåññó [7].…”

“…Óñ-òàíîâëåíî, ÷òî íàðÿäó ñ àêòèíîâûìè ìèêðîôèëàìåí-òàìè âàaeíóþ ðîëü â îáåñïå÷åíèè êëåòî÷íîé ïîäâèae-íîñòè èãðàþò ìèêðîòðóáî÷êè. Áîëåå òîãî, ôóíêöèîíè-ðîâàíèå àêòèíîâûõ ìèêðîôèëàìåíòîâ çàâèñèò îò ïî-ëèìåðèçàöèîííîé äèíàìèêè ìèêðîòðóáî÷åê [2].Ðàíåå íàìè ïîêàçàíî, ÷òî â èíâàçèâíîì ôðîíòå êî-ëîðåêòàëüíîãî ðàêà ïîâûøåíà ýêñïðåññèÿ b III -òóáóëè-íà [9]. Çàòåì, ïðîâåäÿ ñðàâíåíèå ñ ýêñïðåññèåé b I -àöå-òèëèðîâàííîãî è òèðîçèíèðîâàííîãî a-òóáóëèíîâ, ìû óñòàíîâèëè, ÷òî èìåííî b III -òóáóëèí àññîöèèðîâàí ñ ôåíîìåíîì îïóõîëåâîãî ïî÷êîâàíèÿ, êîòîðûé, â ñâîþ î÷åðåäü, ïðåäñòàâëÿåò ñîáîé ïóë êëåòîê, íåïîñðåäñò-âåííî îñóùåñòâëÿþùèõ èíôèëüòðàòèâíûé ðîñò [1].…”